Analysis of the association of IL1B(C-511T) polymorphism with dental implant loss and the clusterization phenomenon

Objectives: Endosteous dental implants consist in the treatment of choice to replace tooth loss. The knowledge that implant loss tends to cluster in subsets of individuals may indicate that host immune‐inflammatory response is influenced by genetic factors. Interleukin‐1 (IL‐1) is a key mediator of inflammatory processes and functional polymorphisms in IL1 gene could be candidate genetic risk factors to study susceptibility to implant failure. The objective of this study was to investigate the association between IL1B (C‐511T) genetic polymorphism and dental implant loss in a Brazilian population and its influence in the clusterization phenomenon. Material and methods: The sample composed of 277 unrelated, both gender, mean age 53.63 ± 11.14 years individuals, divided into test group – 92 subjects with implant loss, and control group – 185 subjects with no implant loss. Patients' socioeconomic profile and clinical variables were investigated. Genomic DNA from oral mucosa was analyzed by polymerase chain reaction–restriction fragment length polymorphism. Results: There was significant difference between the groups in medical treatment (P=0.040), edentulism (P=0.019), and mean number of placed implants (P=0.001). There was difference between groups with and without implant loss neither considering genotypes (P=0.279) nor alleles (P=0.168) for IL1B (C‐511T) polymorphism. When individuals showing up to one implant failure (n=254) were investigated vs. patients presenting multiple implant loss (n=23), no difference was either observed between groups for genotype (P=0.083) and allele (P=0.838) frequencies. Conclusions: The borderline association of the study polymorphism with implant loss suggests further IL1 haplotype analysis to elucidate the global involvement of IL‐1 proteins in the modulation of the osseointegration process. To cite this article:
Dirschnabel AJ, Alvim‐Pereira F, Alvim‐Pereira CC, Bernardino JF, Rosa EAR, Trevilatto PC. Analysis of the association of IL1B(C‐511T) polymorphism with dental implant loss and the clusterization phenomenon.
Clin. Oral Impl. Res. 22 , 2011; 1235–1241
doi: 10.1111/j.1600‐0501.2010.02080.x     

Association of CD14, IL1B, IL6, IL10 and TNFA functional gene polymorphisms with symptomatic dental abscesses

AIM: To investigate in individuals with symptomatic dental abscesses the occurrence of functional polymorphisms within five genes involved with the immune response. The functional gene polymorphisms analysed were CD14 (-260 C/T), IL1B (+3954 C/T), IL6 (-174 G/C,), IL10 (-1082 G/A) and TNFA (-308 G/A). METHODOLOGY: Genomic DNA obtained from oral swabs from individuals with symptomatic dental abscesses and asymptomatic inflammatory periapical lesions, without previous exacerbation, was submitted to restriction fragment length polymorphism (RFLP) analyses to determine each individual genotype. The chi-square and principal components analysis tests were used for statistical analysis. RESULTS: A significant association was observed between the occurrence of the GG genotype or the G allele expression of the polymorphic locus-174 (G/C) of the IL6 gene, and the presence of the symptomatic dental abscesses in women and in individuals < or =35 years old. The principal components analysis suggested predominance of the symptomatic dental abscesses in individuals displaying: high-producer IL6 genotype; intermediate and high-producer IL1B genotypes and low-producer TNFA genotype. CONCLUSIONS: The present study suggests that genetic factors are associated with susceptibility to develop symptomatic dental abscesses.     

Association of IL1 gene polymorphisms with chronic periodontitis in Brazilians

Chronic periodontal disease (PD) is an infectious immune-inflammatory illness. Polymorphisms in IL1 genes play a role in inflammatory diseases through the modulation of cytokine levels.

Objective

This study aimed to investigate the association between polymorphisms in the IL1 gene cluster and chronic periodontitis in a Brazilian population.

Design

A sample of 113 subjects over 25 years (mean age 41.2) were grouped into: 44 healthy individuals, 31 subjects with moderate and 38 with severe periodontitis. DNA was obtained through a mouthwash and oral mucosa scraping. PCR-RFLP was used to identify the following polymorphisms: IL1A C − 889T (rs1800587), IL1B C − 511T (rs16944), IL1B C + 3954T (rs11436340), IL1RN intron 2 (rs2234663). Differences in the allele/genotype/haplotype frequencies were assessed by Chi-square test (p < 0.05). The risk associated with alleles, genotypes and haplotypes was calculated as odds ratio (OR) with 95% confidence intervals (CI).

Results

Neither IL1A (C − 889T) nor IL1B (C + 3954T) polymorphisms was associated with chronic PD. Allele T for IL1B (C − 511T) only associated with PD in the group of blacks and mulattos. Moreover, genotype 2/2 for IL1RN (intron 2) was associated with severe PD.

Conclusions

Genotype 2/2 of IL1RN for the whole Brazilian population and allele T of IL1B (C − 511T) in a subgroup of Afro-Americans and mulattos were suggested as putative risk indicators for chronic periodontitis.     

Association between interleukin-1 genotype and periodontal disease in a diabetic population

BACKGROUND: Recently, it has become evident that for many common chronic diseases, modifying factors amplify disease mechanisms to make the clinical condition more severe. The aims of this report were 1) to investigate the prevalence of periodontitis in a diabetic population, 2) to evaluate the association of periodontitis with metabolic control, and 3) to evaluate periodontitis in diabetics with different interleukin (IL)-1 genotypes. METHODS: One hundred diabetic patients were screened. Type and duration of diabetes, level of control (glycosylated hemoglobin), and demographic data were recorded. Periodontal disease was defined as two or more teeth with clinical attachment loss (CAL) > or = 5 mm. Poorly controlled diabetes was defined as glycosylated hemoglobin values > 8%. Finger-stick blood samples were collected and analyzed for genotyping of IL-1A (+4845), IL-1B (+3954), IL-1B (-511), and IL-1RN (+2018) polymorphisms. RESULTS: Among the diabetic patients in the study, 66% showed periodontal destruction, and 43% of those could be characterized as severe. The prevalence of severe attachment loss increased with decreasing control of diabetes. Only the IL-1B (-511) genotype was found to be associated with periodontal disease in the African American patients (P<0.05). The frequency of allele 1 was 0.77 in periodontitis affected versus 0.33 in healthy African American diabetics. A borderline significant association between IL-1B (+3954) and periodontal disease also was noted in Caribbean periodontal patients (P=0.06); however, the allele 2 frequency in this population was only 10%. CONCLUSIONS: These data confirm the high prevalence and severity of periodontitis in the diabetic population, and support the association between poor glycemic control and periodontal disease. The low prevalence of some of the IL-1 gene polymorphisms in the ethnic groups included in this study limits the validity of conclusions on genotype associations with clinical findings, but there was a trend suggesting that allele 1 at IL-1B (-511) and IL-1B (+3954) was overrepresented among diabetics with periodontal disease.     

Association of interleukin-1 receptor antagonist gene polymorphisms with early onset periodontitis in Japanese

BACKGROUND/AIMS: Early onset periodontitis (EOP), newly 'aggressive periodontitis', is considered to have genetic basis, which have not been clearly defined. The interleukin-1 (IL-1) gene cluster polymorphism as one of genetic factors may influence the expression of several chronic inflammatory diseases. The aim of this study is to investigate the frequency of single nucleotide polymorphisms (SNPs) in the genes encoding IL-1alpha, IL-1beta and a variable number of tandem repeat (VNTR) polymorphisms in the IL-1 receptor antagonist gene (IL-1RN) in 47 generalized EOP (G-EOP) patients and 97 periodontally healthy controls. MATERIAL AND METHODS: All subjects were of Japanese descent and systemically healthy. They were identified according to established clinical criteria. SNPs in the IL-1alpha (+ 4845) and IL-1beta (- 511, + 3954) genes were analyzed by amplifying the polymorphic region using polymerase chain reaction (PCR), followed by restriction-enzyme digestion and agarose gel electrophoresis. IL-1RN (VNTR) polymorphisms were then detected by PCR amplification and fragment size analysis. RESULTS: There was no significant difference in the IL-alpha (+ 4845) and IL-1beta (- 511, + 3954) genotypes and allele frequencies between G-EOP patients and healthy controls. However, the frequency of IL-1RN (VNTR) polymorphic alleles was found to be significantly increased in G-EOP patients (chi2 test, P = 0.007; odds ratio = 3.40). Additionally, the carriage rate of IL-1RN (VNTR) polymorphisms was significantly higher in G-EOP patients than in healthy controls (chi2 test, P = 0.005; odds ratio = 3.81). CONCLUSION: These findings suggest that IL-1RN (VNTR) polymorphisms are associated with G-EOP in Japanese.     

A functional interleukin-1 beta gene polymorphism is associated with chronic periodontitis in a sample of Brazilian individuals

BACKGROUND: Interleukin-1 beta (IL-1 beta) is a potent inflammatory mediator and an important polymorphism in the locus +3954 (C/T) of the human IL1 B gene has been shown to affect the levels of this cytokine. This functional polymorphism has been associated with the establishment of inflammatory diseases, including periodontal disease, in European, Asian and North American populations. OBJECTIVE: The aim of this study was to investigate the association between the IL1 B (+3954) gene polymorphism and the occurrence of different clinical forms of periodontitis in a sample of Brazilian individuals. METHODS: This study employed a cross-sectional design involving individuals from the State of Minas Gerais in the south-eastern region of Brazil. Genomic DNA was obtained from oral swabs of 129 individuals and amplified using the polymerase chain reaction (PCR) with specific primers flanking the locus +3954 of IL1 B. PCR products were submitted to restriction endonuclease digestion and analyzed by polyacrylamide gel electrophoresis, to distinguish alleles T and C of the IL1 B gene, allowing for the determination of the genotypes and detection of the polymorphism. RESULTS AND CONCLUSIONS: The chronic periodontitis group displayed a higher percentage of the T allele (28%) when compared to the aggressive periodontitis group (10.7%, chi(2)=5.24, p=0.02, OR=0.31, CI=0.11--0.88) and to control group (8.7%, chi(2)=7.11, p=0.007, OR=0.24, CI=0.08--0.73). Our data suggested that the polymorphism in the locus +3954 of IL1 B gene could be a risk factor for chronic periodontitis in a sample of Brazilian individuals.     

Distribution of interleukin-1beta(+3954) and IL-1alpha(-889) genetic variations in a Thai population group

BACKGROUND: The severe form of chronic periodontitis (CP) has been reported to be strongly associated with the presence of allele 2 of composite IL-1beta(+3954) and IL-1alpha(-889) genetic polymorphisms (genotype positive). However, other studies have reported conflicting findings, not only on the association between the composite IL-1 gene polymorphisms and CP, but also the link between IL-1 gene polymorphisms and aggressive periodontitis (AgP). These might have resulted from differences in ethnic background and disease entities. The aim of this study was to determine the distribution of IL-1beta(+3954) and IL-1alpha(-889) genetic polymorphisms in a group of Thai subjects based on their periodontal status, including CP, AgP, and healthy groups. METHODS: A total of 123 Thai subjects were clinically and radiographically assessed for their periodontal status. Blood samples were collected by fingerstick and adsorbed onto filter paper. The IL-1beta(+3954) and IL-1alpha(-889) genotypes were performed by polymerase chain reaction, digested with restriction enzymes, and separated by gel electrophoresis. RESULTS: The distribution of allele 1 homozygous genotype was 97.6% and 84.6% for IL-1beta(+3954) and IL-1alpha(-889), respectively. No allele 2 homozygous genotype was detected in either of these two gene loci. Only 1.6% (2 out of 123) of the subjects were genotype positive, which was too low to determine the association between the composite genotype of IL-1beta(+3954) and IL-1alpha(-889) and severe forms of periodontal disease. CONCLUSION: Genetic polymorphism of IL-1 genes in these two loci may not be useful in predicting the severity of periodontal disease in the Thai ethnic group.     

Genetic and immunological markers predict titanium implant failure: a retrospective study

This study evaluates diagnostic markers to predict titanium implant failure. Retrospectively, implant outcome was scored in 109 subjects who had undergone titanium implant surgery, IL1A ?889 C/T (rs1800587), IL1B +3954 C/T (rs1143634), IL1RN +2018 T/C (rs419598) and TNFA ?308 G/A (rs1800629) genotyping, in vitro IL-1β/TNF-α release assays and lymphocyte transformation tests during treatment. TNF-α and IL-1β release on titanium stimulation were significantly higher among patients with implant loss (TNF-α: 256.89 pg/ml vs. 81.4 pg/ml; p < 0.0001; IL-1β: 159.96 pg/ml vs. 54.01 pg/ml; p < 0.0001). The minor alleles of the studied polymorphisms showed increased prevalence in the implant failure group (IL1A: 61% vs. 42.6% in controls, IL1B: 53.7% vs. 39.7% in controls, TNFA: 46.3% vs. 30.9% in controls, IL1RN: 58.5% vs. 52.9% in controls). Increasing numbers of risk genotypes of the studied polymorphisms were associated with an increasing risk of implant loss, suggesting an additive effect. Multiple logistic regression analysis showed positive IL-1β/TNF-α release assay scores (p < 0.0001, OR = 12.01) and number of risk genotypes (p < 0.046, OR = 1.57–6.01) being significantly and independently associated with titanium implant failure. IL-1/IL1RN/TNFA genotyping and cytokine release assay scores provide prognostic markers for titanium implant outcome and may present new tools for individual risk assessment.     

Polymorphisms within the IL-1 gene cluster: effects on cytokine profiles in peripheral blood and whole blood cell cultures of patients with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis

BACKGROUND: Genetic polymorphisms of cytokines have been associated with the susceptibility, severity, and clinical outcome of inflammatory diseases, such as periodontitis and chronic arthritis. An important question to address is how interleukin (IL)-1 polymorphisms affect the cytokine profiles of patients with such diseases. METHODS: The study population consisted of Danish white adults, <35 years of age, who were diagnosed with localized aggressive periodontitis (LAgP, n = 18), generalized aggressive periodontitis (GAgP, n = 27), juvenile idiopathic arthritis (JIA, n = 10), and rheumatoid arthritis (RA, n = 23) and healthy individuals with no systemic or oral diseases (n = 25). Genotypes of IL-1A-889, IL-1A+4845, IL-1B-511, and IL-1B+3954 were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and IL-1RN variable number tandem repeat (VNTR) was detected by PCR amplification and fragment size analysis. Analysis of variance was used to evaluate the effects of IL-1 genotypes on the levels of IL-1alpha, -1beta, -1 receptor antagonist, -6, and -10; tumor necrosis factor-alpha (TNF-alpha); and lymphotoxin-alpha in peripheral blood (plasma) and in unstimulated and stimulated whole blood cell cultures from the same blood collection. RESULTS: The frequencies of IL-1 genotypes investigated did not differ significantly between diseased and control individuals. In LAgP patients, allele 2 of IL-1RN VNTR was associated with significantly higher levels of IL-1alpha, -6, and -10 and TNF-alpha, whereas allele 2 of IL-1B+3954 was associated with significantly lower levels of the same cytokines. In GAgP patients, a general lack of association was found. In JIA and RA patients, IL-1RN VNTR also influenced the cytokine levels. CONCLUSIONS: IL-1 genotypes were associated with cytokine levels in patients with aggressive periodontitis and chronic arthritis. No associations were observed in control individuals.     

No correlation of five gene polymorphisms with periodontal conditions in a Greek population

BACKGROUND: Various studies have examined possible correlations between a number of cytokine gene polymorphisms and periodontal disease in populations of different origins. The present study sought the correlation between four single-nucleotide polymorphisms (IL1A+3954, IL1B+4845, TNFA-308, COL1A1 Sp1), a variable number of tandem repeats polymorphism (IL1RN intron 2) and periodontal conditions in subjects of Greek origin. METHODS: One hundred and ninety-two healthy subjects, stratified as non-periodontitis and periodontitis (chronic and aggressive) cases, participated in the present study. Genotyping was performed by polymerase chain reaction-based techniques using the primers and conditions described in the literature. The frequencies of genotypes between study groups were compared using Genepop v3.3 genetic software and Instat statistical package. RESULTS: No differences were observed among the groups concerning the distributions of genotypes under investigation. CONCLUSIONS: Carriage rates of the polymorphisms under investigation in systemically healthy subjects of Greek origin are well within the range reported for Caucasians but these polymorphisms cannot discriminate between non-periodontitis and periodontitis (chronic or aggressive) cases.     

Association of interleukin-1 polymorphisms with periodontitis in Down syndrome

This study examined the association of IL1 genetic polymorphisms (IL-1A +4845, IL-1B +3954 & IL-1RN +2018) with periodontal disease status of Down syndrome (DS) individuals. Fifty-four DS patients (18-56 yr, 48.15% male, 77.78% Caucasians) were recruited from the Georgia Regional Hospital (GRH) health care system. Two comparable groups (71 mentally retarded patients and 87 control subjects) were also recruited. All subjects were nonsmokers. Periodontal evaluations (plaque index, gingival index, bleeding-on probing and clinical attachment levels (AL)), personal and professional dental care habits were recorded. Blood was collected by a venipuncture. The IL-1A +4845, IL-1B +3954 & IL-1RN +2018 loci were genotyped by the TaqMan assay. No statistically significant differences were noted in the distribution of IL-1 gene polymorphisms between the three groups. The IL-1 variant genotypes varied by race; for both IL-1A and IL-1RN, the variant gene was significantly more prevalent among whites than non-whites (ps > 0.1). ANCOVA, which also adjusted for age, showed a 3-way interaction among dental visits, gene variation and Down status [(F(1, 179) = 3.96, P = 0.048 in White subjects and F(1, 241) = 2.96, P = 0.087 in all subjects). Post-hoc t-tests confirmed lower levels of AL in IL-1RN-variant Down subjects receiving more frequent dental visits (P < 0.05). ANCOVA, which also adjusted for age, showed an interaction between IL-1A/B gene variation and Down status (F(1, 174) = 3.04, P = 0.083 in White subjects and F(1, 235) = 3.72, P = 0.055 in all subjects). Post-hoc t-tests confirmed lower levels of AL in IL-1A/B-variant Down subjects (P < 0.05). The distribution of variant IL-1 genes in DS subjects was not different from the general population. However the association between the carriage of the IL-1 rare alleles and periodontitis differed between the Down and non-Down subjects. The carriage of the IL-1 rare alleles in the Down subjects tended to confer a protective effect against loss of periodontal attachment.     

Association analysis between interleukin-1 family polymorphisms and generalized aggressive periodontitis in a Chinese population

BACKGROUND: It has been suggested that aggressive periodontitis (AgP) has a genetic basis, but this theory has not been confirmed. The intent of this investigation was to study whether specific interleukin (IL)-1 genotypes and/or alleles could be used to predict susceptibility to generalized AgP (GAgP) in Chinese. METHODS: The GAgP group consisted of 122 patients, and the control group included 95 healthy subjects. Single nucleotide polymorphisms at IL-1A (+4845) and IL-1B (-511, +3954) were analyzed by standard polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The polymorphism of a variable number tandem repeat (VNTR) in intron 2 of IL-1RN was detected by PCR amplification and fragment size analysis. RESULTS: There was no significant association of IL-1 polymorphisms with GAgP in the unstratified subjects. However, when cases were stratified by gender, the frequencies of A2+ genotype and allele 2 at IL-1A +4845 were significantly increased in male patients compared to male controls (genotype: odds ratio [OR] 5.58, 95% confidence interval [CI]: 1.09 to 28.68, P = 0.039; allele: OR 4.97, 95% CI: 1.01 to 24.50, P = 0.049; adjusted for age and smoking status). The frequency of IL-1B -511 A1/A2 heterozygote was significantly increased in male GAgP group compared to male controls (adjusted OR 3.16, 95% CI: 1.01 to 9.89, P = 0.048). In females, no significant differences were found between patients and controls in corresponding analyses at all polymorphic loci. A possible combined effect of IL-1B -511 polymorphism and smoking on the elevated risk to GAgP was observed. The OR of GAgP for combined A2+ genotype and smoking was 12.45 (95% CI: 1.43 to 108.06, P = 0.022), and for combined allele 2 and smoking was 18.25 (95% CI: 2.32 to 143.86, P = 0.006). CONCLUSIONS: The polymorphisms of IL-1A +4845 and IL-1B -511 may play an important role in determining GAgP susceptibility in Chinese males. Furthermore, a possible combined effect of the polymorphism of IL-1B -511 and smoking on GAgP susceptibility was suggested.     

Interleukin-1 genotypes and the association between periodontitis and cardiovascular disease

An epidemiological association between periodontitis and cardiovascular disease has been reported in multiple studies. Various mechanisms have been proposed as potential explanations for this association, including a common factor that predisposes certain individuals to a hyper-responsive inflammatory response. Variations in the genes that regulate the interleukin-1 (IL-1) response have been associated with both periodontal disease and cardiovascular disease. New data indicate that one pattern of IL-1 genetic polymorphisms, characterized by the IL-1A (+4845) and IL-1B (+3954) markers, is associated with periodontitis but not certain measures of atherosclerosis. Another IL-1 genetic pattern, characterized by the IL-1B (-511) and IL-1RN (+2018) markers, is associated with atherosclerotic plaque formation, as measured by angiography and arterial wall thickness, but not periodontitis. These two patterns also have different functional implications relative to IL-1 biological activity. Studies of IL-1 gene polymorphisms, atherosclerotic plaque instability and cardiovascular clinical events are in progress. Hypothetical models are presented to explain how IL-1 genetic factors may be involved in cardiovascular disease.     

Polymorphisms of the interleukin-1 gene family, oral microbial pathogens, and smoking in adult periodontitis

Interleukin (IL)-1alpha, IL-1beta, and IL-1ra contribute to regulation of the inflammatory response in periodontal tissues. We aimed to investigate the distribution of polymorphisms in the IL-1 gene family among periodontitis patients and controls, taking into account smoking and microbiology as additional variables. Fifty-three non-smoking and 52 smoking patients with severe adult periodontitis and 53 controls were genotyped for bi-allelic IL-1A(-889), IL-1B(-3954), and a penta-allelic 86-bp VNTR IL-1RN gene polymorphisms. The presence of Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans was established by culture techniques. We found a higher frequency of allele 2 carriage in IL-1A, IL-1B, and IL-1RN in periodontitis patients who were non-smokers and in whom P. gingivalis and A. actinomycetemcomitans could not be detected (42.1% vs. 11.3% in controls; P = 0.0068; OR 5.7, 95% CI: 1.6-19.8). Our results provide evidence that polymorphisms in genes of the IL-1 family are associated with severe adult periodontitis in the absence of other risk factors tested in this patient population.     

Evaluation of the relationship between interleukin-1 gene cluster polymorphisms and early implant failure in non-smoking patients

OBJECTIVE: The aim of the present study was to investigate the relationship between specific polymorphisms of the interleukin-1 gene cluster and the early failure of osseointegrated implants. MATERIAL AND METHODS: The subject population was composed by a test group comprising 28 non-smoking patients (mean age 52.7) that had suffered one or more early implant failures and by a control group consisting of 34 individuals (mean age 43.3) with one or more healthy implants. Genomic DNA from buccal mucosa was amplified by the polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP) and submitted to polyacrylamide gel electrophoresis to distinguish the alleles of the interleukin-1A (-889), interleukin-1B (+3953), interleukin-1B (-511) and interleukin-RN (intron 2) gene polymorphisms. Differences in the allele and genotype frequencies between control and test groups were assessed by chi(2) test or by Monte Carlo simulations (P<0.05). Haplotype frequencies, linkage disequilibrium and Hardy-Weinberg equilibrium were also estimated. RESULTS: No statistically significant differences were found in the genotype distribution or allelic frequencies of the polymorphisms. No differences were observed between control and test groups when different interleukin-1 gene cluster haplotypes were compared. Nevertheless, the interleukin-1A (-889) and interleukin-1B (+3953) polymorphic sites were in strong linkage disequilibrium (P=0.00014 for control group and P=0.0238 for the test group). CONCLUSION: This study suggests that polymorphisms in the interleukin-1 gene cluster are not associated with early implant failure in a non-smoking Brazilian population.     

Interleukin-1 and tumor necrosis factor-alpha gene polymorphisms in Turkish patients with localized aggressive periodontitis

Localized aggressive periodontitis (LAgP) is a complex multifactorial periodontal disease to which genetic factors are thought to predispose individuals. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are potent immunomodulators and proinflammatory cytokines that have been implicated in the pathogenesis of autoimmune and infectious diseases and proposed to be risk factors for LAgP. Our aim was to investigate IL-1 alpha (+4845), IL-1 beta (+3954), and TNF-alpha (-308) gene polymorphisms in Turkish LAgP patients. We genotyped 31 LAgP patients and 31 healthy controls for IL-1alpha(+4845), IL-1beta(+3954), and TNF-alpha(-308) using standard PCR amplification followed by restriction enzyme digestion and gel electrophoresis. Higher prevalence of heterozygosity for IL-1alpha(+4845) was found in cases (65%) when compared to controls (35%) (P < 0.05). While homozygous allele 1 of IL-1beta(+3954) was the most frequent genotype in cases (62%), no controls were homozygous for this allele (P < 0.001). Homozygous allele 1 was the most common TNF-alpha genotype in both groups, however no significant difference in TNF-alpha genotypes was found between groups. In conclusion, in this Turkish population, susceptibility to LAgP is increased by heterozygosity for allele 1 of IL-1alpha(+4845) or homozygosity for allele 1 of IL-1beta(R+3954). Moreover, IL-1 gene polymorphisms appear to have a role in susceptibility to LAgP, and the above-mentioned genotypes could be an important risk factor for LAgP in the Turkish population.     

白细胞介素-1基因多态性与侵袭性牙周炎的关系

目的：研究中国人群中白细胞介素-1（IL-1）基因多态性与侵袭性牙周炎（AgP）之间的关系。方法：提取122例AgP患者和95例健康对照者外周静脉血基因组DNA,采用聚合酶链反应（PCR）分析IL-1A＋4845、IL-1B＋3954位点的单核苷酸多态性（SNP）及IL-1RN第二内含子中的可变数目重复序列（VNTR）多态性,采用多因素Logistic回归模型,进行两组之间基因型、等位基因分布差异的比较。结果：在IL-1A＋4845位点,AgP组男性患者A2^＋基因型的频率较男性健康组显著升高（P〈0．05=0．039）,等位基因A2的携带率也显著升高（P〈0．05=0．049）;未发现IL-1B＋3954位点和IL-1RN VNTR的多态性与AgP关联;未发现IL-1各复合基因型与AgP存在明显关联性。结论：IL-1A＋4845位点的SNP可能与中国人群中男性个体的AgP易感性有关。     

Analysis of association of clinical aspects and vitamin D receptor gene polymorphism with dental implant loss

Osseointegration failure is a complex, multifactorial trait shown to concentrate in some treated populations. There has been shown evidence for genetic contribution to dental implant loss. Genetic polymorphisms have been classically considered as genetic risk factors for several diseases and, more recently, for dental implant loss.
Objectives: The purpose of this study was to access clinical factors related to failure process, and to investigate the relationship between a vitamin D receptor (VDR) polymorphism (rs731236, Taq I) and dental implant loss.
Material and methods: Two hundred and seventeen unrelated patients, mean age 51.7±11.3 years, were divided into two groups: (i) control group (C), 137 individuals presenting at least one osseointegrated implant in function for 6 months or more and without any implant loss, and (ii) study group (S), 80 individuals presenting at least one implant loss. After DNA collection and purification, VDR Taq I polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). Differences between C and S, and between healthy (H; n =1232) and lost (L; n =135) implants were accessed.
Results: Positive evidence of association has been detected between implant loss and the following variables: edentulism, implant position, primary stability, and implant length. Cox's regression model showed that primary stability, surgical technique and bone quantity were related to implant survival over time. No association between genotypes or alleles of VDR Taq I polymorphism and implant loss was found between the groups.
Conclusion: It was observed that clinical variables, but not the study polymorphism, were associated with dental implant loss.     

IL-1基因多态性与牙周炎关系的研究

目的:研究中国汉族人IL-1 基因多态性与牙周炎易感性的关系。方法:收集30 例重度成人牙周炎(AP) 患者、20 例快速进展型牙周炎(RPP) 患者和94 例健康对照者的颊粘膜拭子,抽提DNA ,PCR-RELP 方法检测IL-1 基因簇基因多态性,比较三组患者各等位基因检出率的差异。结果:AP 组和RPP 组IL-1B + 3953PTaqI 等位基因Ⅱ的检出率均显著高于对照组(APP对照组OR = 618 ,RPPP对照组OR = 916 , P < 0105) ,AP 组IL-1RN 内含子2PVNTR 等位基因Ⅱ的检出率也显著高于对照组( OR = 613 , P < 0105) 。IL-1A-889PNcoI 等位基因在三组间的分布无显著性差异( P > 0105) 。结论:中国汉族人中携带IL-1B + 3953PTaqI 等位基因Ⅱ和IL-1RN 内含子2PVNTR 等位基因Ⅱ可能是牙周炎的遗传易感因素;AP 和RPP 存在遗传异质性。     

Association of interleukin-1 polymorphisms with periodontal disease

BACKGROUND: Several studies have investigated genetic polymorphisms for cytokines as potential genetic markers for periodontitis. Some studies have found that interleukin (IL)-1A and IL-1B polymorphisms are associated with a higher severity of periodontitis, while others found no association. The aims of this study were to determine the prevalence of the IL-1A-889 and IL-1B+3954 (previously described as +3953) polymorphisms in Chileans and their association with periodontitis. METHODS: Subjects aged 20 to 48 were selected from people requesting dental treatment at a public health center in Santiago, Chile. A case-control study of 330 cases of periodontitis patients and 101 healthy controls was performed. A full-mouth periodontal examination was performed on each subject and a structured questionnaire was conducted to determine smoking habits. Cases were categorized as having initial, moderate, or severe periodontitis according to the percentage of sites with clinical attachment loss > or =3 mm. Genomic DNA was analyzed for polymorphism in the IL-1A gene at site -889 and IL-1B gene at site +3954 by polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion and gel electrophoresis. Data were analyzed by chi square test, analysis of variance (ANOVA), and by calculating odds ratio (OR) and 95% confidence intervals (CI). RESULTS: Demographic and socio-economic characteristics of subjects were similar in cases and in controls. A higher frequency of heterozygous of the IL-1A-889 was found in cases than in controls, but the difference was not significant. The heterozygous of the IL-1B+3954 was significantly higher in cases than in controls and was associated with periodontitis (OR 3.12, 95% CI 1.59 to 6.09, P = 0.001). The homozygous for allele 1 of the IL-1B+3954 was a protective factor for periodontitis (OR 0.35, 95% CI 0.19 to 0.66, P = 0.001). The prevalence of positive genotype (at least one allele 2 present at each locus) was significantly higher in cases (26.06%) than in controls (9.9%) and was significantly associated with periodontitis (OR 3.21, 95% CI 1.60 to 6.44, P = 0.001), irrespective of the smoking status and periodontitis severity. Sensitivity of positive genotype was 26%, the specificity 90%, and the positive predictive value 89%. CONCLUSION: Within the limits of this study, the results show that individuals carrying the positive genotype have significantly greater risk for developing periodontitis.