Association of (-1,607) 1G/2G polymorphism of matrix metalloproteinase-1 gene with knee osteoarthritis in the Turkish population (knee osteoarthritis and MMPs gene polymorphisms)

The aim of this study was to investigate whether functional polymorphisms in the promoter of matrix metalloproteinase-1 (MMP-1), MMP-2 and MMP-9 genes were associated with susceptibility to knee osteoarthritis in the Turkish population. The MMP-1 −1,607 1G/2G (rs1799750), MMP-2 −1,306 C/T (rs243865), and MMP-9 −1,562 C/T (rs3918242) polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism assay in 157 patients diagnosed with knee osteoarthritis based on the criteria of American College of Rheumatology and in 84 controls in Mersin, Turkey. Genotype distributions and allele frequencies of MMP-1, MMP-2, and MMP-9 gene polymorphisms were compared between the patients and controls. There were significant differences between the groups regarding the genotype distribution of MMP-1 polymorphism (P  = 0.001). The frequencies of 1G/1G and 1G/2G genotypes were significantly higher in the knee osteoarthritis than in the controls (P = 0.002, and P =  0.006, respectively). In addition, 1G allele frequency of MMP-1 gene was higher in the patients than in the control group (P = 0.0001). The genotype distributions and allele frequencies of MMP-2 and MMP-9 gene polymorphisms did not differ between the osteoarthritis and the control groups (P > 0.05). These findings suggest that the −1,607 1G/2G polymorphism in the MMP-1 gene may contribute to susceptibility to knee osteoarthritis in the Turkish population.     

Stromelysin-1 (MMP-3) gene 5A/6A promoter polymorphism is associated with blood pressure in a community population

BACKGROUND AND OBJECTIVES: Arterial remodelling contributes to the development of hypertension. Stromelysin-1 (MMP-3), a member of the matrix metalloproteinase family may contribute to this process. Stromelysin-1 gene expression is partly regulated by a common polymorphism in the promoter region of either five or six consecutive adenosine bases (5A/6A). METHODS AND RESULTS: A cross-sectional study of 1111 randomly selected male and female community subjects (27-77 years), were assessed for conventional cardiovascular risk factors and stromelysin-1 5A-1171-6A genotype. Multivariate analysis showed an independent association between the stromelysin-1 genotype and blood pressure that was recessive for the 5A/5A genotype. Subjects with the 5A/5A genotype had a higher mean systolic blood pressure (SBP) (+4.2 mmHg) and diastolic blood pressure (DBP) (+2.2 mmHg) compared to subjects with 5A/6A and 6A/6A genotypes. Subgroup analysis revealed an independent association of the 5A/5A genotype with SBP (+3.6 mmHg, P = 0.001) and DBP (+2.0 mmHg, P = 0.004) in subjects not on blood pressure medication. Whereas subjects with the 5A/5A genotype and taking medication had a higher mean SBP (+7.4 mmHg, P = 0.02) and DBP (+2.7 mmHg, P = 0.11). Multivariate analysis in the whole population showed there was no association between genotypes and mean intimal-medial wall thickness (IMT) (P = 0.87) or the likelihood of carotid plaque formation. CONCLUSIONS: The stromelysin-1 5A-1171-6A genotype is an important determinant of blood pressure in this general population sample.     

Serum matrix metalloproteinase-3 concentration is influenced by MMP-3 -1612 5A/6A promoter genotype and associated with myocardial infarction

OBJECTIVES. Matrix metalloproteinase-3 (MMP-3) is implicated in the formation of atherosclerotic plaques, and the MMP-3 -1612 5A/6A polymorphism is associated with myocardial infarction (MI) and stable coronary artery disease (CAD). The present study examined whether the -1612 5A/6A polymorphism in the promoter region of the MMP-3 gene influences serum concentrations of MMP-3 and whether serum concentrations of MMP-3 are related to extent of coronary atherosclerosis and risk of MI. DESIGN AND SUBJECTS. This case-control study was conducted in three hospitals in the northern part of Stockholm. A total of 755 MI patients aged below 60 were screened, 433 entered and 387 completed the study. Three hundred and eighty-seven sex- and age-matched control subjects were recruited from the general population of the same county. METHODS. The MMP-3 genotype was determined by Pyrosequencing(TM) and the serum MMP-3 concentration was quantified with an immunoassay. Severity and extension of CAD was assessed by quantitative coronary angiography in a subgroup of patients (n=243). RESULTS. Patients had lower serum MMP-3 concentration than controls. There was a strong association between MMP-3 -1612 5A/6A genotype and serum concentrations of MMP-3. The presence of one or two copies of the 6A-allele was associated with a graded increase in serum MMP-3. In female patients there was an inverse correlation (r=-0.39, P<0.05) between serum MMP-3 concentration and plaque area. Conclusion. In conclusion, the serum concentration of MMP-3 is influenced by MMP-3 -1612 5A/6A genotype and associated with MI.     

基质金属蛋白酶-3基因启动子5A/6A多态性与高血压病的关系

目的探讨基质金属蛋白酶-3(MMP-3)基因启动子-1171(5A/6A)多态性对兰州地区汉族人群高血压病发病的可能影响。方法采用限制性片段长度多态性分析技术,检测高血压病患者(高血压病组,104例)和正常者(对照组,102例)MMP-3基因启动子SNP-1171(5A/6A)基因型的分布。结果高血压病组与对照组MMP-3基因型分布差异无统计学意义,按性别分组比较两组男性、女性之间差异均无统计学意义(P<0.05),Logistic回归分析发现男性50岁以下病例组与对照组比较差异有统计学意义(P=0.013)。并且患高血压的危险性将增加5.97倍。不同血压分级之间基因型分布和等位基因频率比较无差异(分别为P=0.950,P=0.885)。结论MMP-3基因启动子-1171(5A/6A)多态性对高血压病发病的影响与性别年龄有关,与血压水平无关。     

A SMAD3 gene polymorphism is related with osteoarthritis in a Northeast Chinese population

Variants in the SMAD family member 3 (SMAD3) have recently been reported to be associated with osteoarthritis (OA) in European populations. However, the results are contestable. To assess the role of such variants in SMAD3 in OA susceptibility in peripheral joints OA, we conducted a case–control study in a Northeast Chinese population. The SMAD3 SNP was genotyped in patients who had primary symptomatic OA with radiographic confirmation and clinical symptom and in controls, and the associations were examined. A total of 111 knee OA patients, 121 hand OA patients and 236 controls were genotyped. Statistically significant difference was detected in genotype and allele frequencies between OA and control groups in the population. There were significant association for knee OA OR = 3.68 (95 % CI 2.03–6.70; p < 0.001) and for hand OA OR = 3.60 (95 % CI 2.01, 6.44; p < 0.001). The association was also positive even after stratification by sex except for male population of knee OA. Our data indicated that genetic variation in the SMAD3 gene is involved in pathogenesis of both knee OA and hand OA in Northeast Chinese population, which is consistent with in European populations.     

Association of TIMP-4 gene polymorphism with the risk of osteoarthritis in the Korean population

Due to an imbalance in the MMP:TIMP ratio determined a tissue damage in arthritis, it is hypothesized that polymorphic variations of the TIMP genes are associated with regulation of the MMP:TIMP balance. To test this hypothesis, the presence of single nucleotide polymorphisms (SNPs) located in the human TIMP-2 and TIMP-4 genes was confirmed in the Korean RA and OA patients. We performed a case-control study comprising 109 unrelated Korean OA patients, 177 unrelated Korean RA patients and 175 healthy subjects. There were statistically significant differences in the genotype distribution and allele frequencies of the C/T polymorphism of TIMP-4 gene between OA and control groups (P = 0.0002 and P = 0.001, respectively). However, no significant association between TIMP-2 polymorphisms and OA was observed. Also, no difference was observed when allele or genotype frequencies of both TIMP-2 and TIMP-4 gene polymorphisms were compared between RA and controls. We demonstrated that the C/T polymorphism which is located on the 3'-untranslational regions of the TIMP-4 gene might be associated with susceptibility to OA patients.     

Association of radiographic hand osteoarthritis with radiographic knee osteoarthritis after meniscectomy

OBJECTIVE: To evaluate the association between radiographic hand osteoarthritis (OA), a disease with marked heredity, and radiographic knee OA in patients treated with meniscectomy. METHODS: We retrospectively identified 170 patients (mean age 54 years [range 33-87 years], 23% women) who had undergone isolated meniscectomy an average of 20 years earlier (range 17-22 years). Patients with cruciate ligament injury were excluded. All subjects were examined by standardized knee and hand radiography. Individual joints were considered to have OA when displaying radiographic features corresponding to a Kellgren/Lawrence (K/L) grade > or =2. Hand OA was considered present if at least 1 of the following criteria was fulfilled: the presence of radiographic OA (K/L grade > or =2) in at least 1 interphalangeal joint in each hand symmetrically, or in at least 2 distal or proximal interphalangeal joints in the same hand in a pattern consistent with primary OA (in the same row or ray), or in the first carpometacarpal joint bilaterally. The association between radiographic hand OA and radiographic knee OA was evaluated using logistic regression. RESULTS: Radiographic hand OA was present in 57 patients (34%) and radiographic knee OA was identified in 105 patients (62%), within 94 index knees (55%) and 47 contralateral knees (28%). In a multivariate model, radiographic hand OA was associated with an increased likelihood of radiographic OA in the index knee (odds ratio [OR] 3.0, 95% confidence interval [95% CI] 1.2-7.5) and in the nonoperated contralateral knee (OR 3.5, 95% CI 1.0-12.2). CONCLUSION: The presence of radiographic hand OA is associated with an increased frequency of radiographic knee OA after meniscectomy. This finding confirms and extends that of a single previous study showing an interaction between hereditary and environmental risk factors for OA, a common and genetically complex disease. Accordingly, the development of OA following a meniscal tear and the resulting meniscal surgery should not be regarded to be of secondary origin only.     

Association of FAS （TNFRSF6）-670 gene polymorphism with villous atrophy in coeliac disease

AIM:To investigate the association of FASgene polymorphism with coeliac disease (CD) development.METHODS: FAS-G670A gene polymorphism, located in a gamma interferon activation site, was studied in 146 unrelated CD patients and 203 healthy ethnically matched controls. The restriction fragment length polymorphism (RFLP) method was used to identify FAS-G670A gene polymorphism.RESULTS:No significant difference was found in genotype frequency between CD cases and controls. In controls,however, the frequency of the GGgenotype was significantly higher in women (26.5%) than in men (12.8%) (OR=2.44,95% CI1.15-5.20, P=0.020) and it was also higher in men with CD than controls (OR=2.60, 95% (CI0.96-7.05, P=0.061).The GG genotype frequency was significantly higher in patients with most severe villous atrophy (Marsh Ⅲc lesions) (OR=3.74, 95% CI 1.19-11.82, P=0.025). A significantly less proportion of men suffered from Marsh IIIc lesions than women (OR=0.20, 95% (CI0.06-0.68, P=0.01). The risk of having severe villous atrophy increased with the additive effect of the Gallele in women (P=0.027 for trend, age and gender adjusted).CONCLUSION: FAS-G670A gene polymorphism is associated with the severity of villous atrophy in CD. Female gender is also associated with the severity of villous atrophy.     

Association of leg muscle symmetry with knee osteoarthritis

Clinical Rheumatology - This study aimed to evaluate the relationship of leg muscle symmetry to the prevalence, radiographic grade, and symptoms of knee osteoarthritis (OA). We conducted a...     

A COL2A1 gene polymorphism is related with advanced stages of osteoarthritis of the knee in Mexican Mestizo population

Primary osteoarthritis (OA) is a multifactorial disease with several genetics factors involved. The COL2A1 gene is of particular interest because it encodes for the most abundant protein in articular cartilage. The aim was to evaluate the association of COL2A1 gene polymorphism with OA of the knee in Mexican Mestizo patients. A case–control study was conducted; cases comprised patients with a radiologic scoring ≥2 and controls with a radiologic scoring <2. DNA was extracted from a peripheral blood sample, the polymorphic site of the COL2A1 gene was submitted to polymerase chain reaction (PCR), and the products were digested using PvuII restriction enzyme. For statistical analysis, a non-conditional logistic regression was developed. There were no associations among alleles in the overall sample, nevertheless, a significant association was found with p (Pp/pp) allele and OA of the knee grade 4 [odds ratio (OR), 95% confidence interval (CI 95%) 4.1 (1.2–14.6)] adjusted by gender, age, and body mass index (BMI). These results suggest an association of a COL2A1 gene polymorphism with advanced stages of OA of the knee in Mexican Mestizo population.     

遵义人群载脂蛋白A5 c.553G/T基因多态性与混合型高脂血症的相关性研究

目的 探讨遵义人群载脂蛋白A5(ApoA5)基因c.553G/T位点多态性与混合型高脂血症的相关性.方法 收集222名遵义地区人群静脉血标本,其中混合型高脂血症组100例,正常对照组122名,用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测两组标本ApoA5基因c.553G/T位点多态性,分析混合型高脂血症组和正常对照组中基因型频率和基因频率分布规律,及其与混合型高脂血症的关系.结果 ApoA5 c.553G/T位点基因型频率和基因频率在混合型高脂血症组与正常对照组差异有统计学意义(x2=12.081,P=0.001;x2=17.469,P＜0.001);通过Logistic回归校正年龄、性别、血糖后,T等位基因携带者(TT+ GT基因型)患高脂血症的风险较GG基因型携带者增加(OR=6.042,95％CI:1.962～18.607,P=0.002).结论 ApoA5 c.553G/T位点多态性与遵义地区人群混合型高脂血症发病存在一定相关性,ApoA5 c.553T等位基因可能是混合型高脂血症的独立危险因素.     

Validation of a modified Thai version of the Western Ontario and McMaster (WOMAC) osteoarthritis index for knee osteoarthritis

The aim of this study was to evaluate the psychometric properties (validity and reliability) of the Thai version of the Western Ontario and McMaster (WOMAC) index in knee osteoarthritis (OA) patients. After permission from the copyright holder of the WOMAC index was obtained, the questionnaire was translated into Thai, backtranslated, tested for face and content validities, and then modified. A convergent validity was evaluated in 114 patients with knee OA by comparing the scores of a modified Thai WOMAC index to those of the algofunctional Lequesne index. A test-retest reliability was evaluated in 89 patients who answered the modified Thai WOMAC index twice at 3-week intervals. The statistical analyses for the content validity were index of content validity (ICV), floor and ceiling effects, and skewness of distribution; for the convergent validity was Spearman's correlation; for the test-retest reliability were Spearman's correlation and intraclass correlation; and for the internal consistency was Chronbach's alpha. The Thai WOMAC index had face validity. The ICV of the content validity ranged from 0.25-1.00. Two items (F05 and F12 of the original 24-item WOMAC index) that had an ICV of 0 were removed from the modified Thai version. The modified 22-item Thai WOMAC index had convergent validity to the algofunctional Lequesne index in pain and function dimensions (Spearman's correlation coefficients were 0.66 and 0.69, respectively). The test-retest reliability had correlation coefficients ranging from 0.65 to 0.71. The internal consistency had an alpha ranging from 0.85 to 0.97. In conclusion, the modified Thai WOMAC index had acceptable psychometric properties for Thai patients with knee OA.     

纤维蛋白原基因G(-455)A多态性与缺血性脑卒中的关系

目的　探讨缺血性脑卒中与纤维蛋白原基因G( 45 5 )A多态性的关系。方法　利用PCR技术和分子杂交技术对北京地区 2 94例缺血性脑卒中患者进行纤维蛋白原基因G( 45 5 )A多态性位点的检测和分析 ,并与 2 79例北京地区的非脑卒中患者进行比较。结果　缺血性脑卒中患者纤维蛋白原基因G( 45 5 )A多态性的基因型频率和等位基因频率与对照组相比无明显差异。结论　纤维蛋白原基因G( 45 5 )A多态性可能不是缺血性脑卒中发病的遗传学危险因素。     

太原市膝骨关节炎的流行病学研究

目的探讨膝骨关节炎（OA）的相关危险因素,以提高膝OA的预防水平。方法参照亚太地区风湿病学会联合会社区控制风湿病规划《膝OA危险因素调查表》（草案）,对太原市某社区2188名居住无电梯6层楼房10年以上的35—64岁居民进行调查。采用logistic回归分析,观察性别、年龄、体重指数、腰围、工龄、受教育程度、吸烟、宗教信仰等因素对膝OA的影响。结果太原市居民膝痛和膝OA患病率分别为13．6％和10、9％,显著高于南方城市汕头,OA患病率与北方城市北京相近;女性患病率显著高于男性（18,3％比8、7％和15．1％比6．3％）,且有随年龄增加而升高的趋势。膝OA患病率在女性40岁以后、男性45岁以后升高更为显著。膝OA组体重指数显著大于非膝OA组。多因素logistic回归分析结果显示：年龄、性别、体重指数为膝OA的危险因素。不同楼层膝痛和膝OA患病率差异无统计学意义。结论地理位置、年龄、女性和超重（体重指数≥24kg／m^2）可能是膝OA的相关危险因素,未发现爬楼梯与膝OA有关联。中年人（尤其是女性）即应开始预防膝OA;控制体重、防止肥胖对预防膝OA有重要意义。     

Association of Fas/Apo1 gene promoter (-670 A/G) polymorphism in Tunisian patients with IBD

AIM: To detect a possible association between the polymorphism of the (-670 A/G) Fas/Apo1 gene promoter and susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population. METHODS: The (-670 A/G) Fas polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: Significantly lower frequencies of the Fas -670 A allele and A/A homozygous individuals were observed in CD and UC patients when compared with controls. Analysis of (-670 A/G) Fas polymorphism with respect to sex in CD and UC showed a significant difference in A/A genotypes between female patients and controls ( P corrected = 0.004 in CD patients and P corrected = 0.02 in UC patients, respectively). Analysis also showed a statistically significant association between genotype AA of the (-670 A/G) polymorphism and the ileum localization of the lesions ( P corrected = 0.048) and between genotype GG and the colon localization ( P corrected = 0.009). The analysis of inflammatory bowel disease patients according to clinical behavior revealed no difference. CONCLUSION: Fas-670 polymorphism was associated with the development of CD and UC in the Tunisian population.     

Association of chemokine CXCL12-3'G801A polymorphism with systemic lupus erythematosus in a Han Chinese population

CXCL12, also known as stromal cell-derived factor (SDF-1), is a CXC chemokine. Recent reports have shown that CXCL12 might play key roles in a murine model of lupus and in patients with systemic lupus erythematosus (SLE). A common variant at position 801 in 3'-untranslated region in CXCL12 gene (designated CXCL12-3'G801A) has been reported in association with autoimmune diseases, such as type 1 diabetes and systemic sclerosis. We investigated the influence of CXCL12-3'G801A polymorphism on susceptibility to SLE by genotyping this single nucleotide polymorphism in 422 SLE patients and 374 healthy controls. The frequency of G/G homozygote was observed in 60.0% of SLE patients and in 52.7% of healthy individuals (χ(2?)=?4.275, p?=?0.039). Compared with patients with G/A and A/A genotype, SLE patients with G/G genotype were also more prone to developing photosensitivity (χ(2?)=?6.778, p?=?0.034), renal damage (χ(2?)=?6.388, p?=?0.041) and to producing antibodies against nucleosomes (χ(2?)=?8.341, p?=?0.015). Moreover, the plasma level of CXCL12α was also significantly increased in patients with G/G homozygote than in healthy controls carrying the same genotype [(4067.0?±?1092.3) pg/ml vs. (3278.5?±?547.4) pg/ml, p?=?0.002]. Our results suggest that polymorphism in CXCL12-3'G801A might be a genetic risk factor for developing SLE. The association of G/G homozygote with nephritis and skin damage developed in SLE patients might be due to its effects upon the production of auto-antibodies and CXCL12 protein.     

A novel variant near LSP1P3 is associated with knee osteoarthritis in the Chinese population

Clinical Rheumatology - Previous genome-wide association study showing a novel variant near LSP1P3 was associated with knee osteoarthritis (KOA) in Caucasians. Replication study in different...     

中国汉族人群APOA5-1131 T/C基因单核苷酸多态性与冠心病的相关性

目的探讨APOA5-1131 T/C单核苷酸多态性与冠心病相关性。方法对经冠状动脉造影的冠心病组168例和对照组160例,采用聚合酶链反应—限制性片段长度多态性（PCR-RFLP）方法检测APOA5-1131 T/C单核苷酸多态性,分析不同基因型与冠心病的关系。结果APOA5-1131 C等位基因频率在冠心病组明显高于对照组（P〈0.01）。相对于T/T基因型,C/C基因型修正后的OR值为2.45,P=0.01;T/C＋C/C基因型的修正后OR值为1.72,P=0.02。结论APOA5-1131 T/C单核苷酸多态性和冠心病的发病密切相关。C/C基因型很可能是冠心病的易感基因型。APOA5-1131 T/C多态性C等位基因可能是中国人群冠心病发病的危险因素之一。     

Association between the -174 C/G polymorphism in the interleukin-6 (IL-6) gene and gastrointestinal involvement in patients with systemic sclerosis

Clinical Rheumatology - Genetic predisposition to systemic sclerosis (SSc) has still not been fully revealed. Interleukin-6 (IL-6) is a mediator of T cell proliferation and fibrotic events in SSc....