MMP2, MMP9 and TIMP2 polymorphisms affect sperm parameters but not fertility in Polish males

Proper function of the blood–testis barrier is pivotal to spermatogenesis. Synchronised action of matrix metalloproteinases (MMP) and their inhibitors (TIMP) is mandatory to maintain dynamic balance of the barrier. Therefore, the association of functional genetic variants of MMP‐2, MMP‐9 and TIMP‐2 and male infertility was studied. A total of 416 infertile males and 421 healthy subjects were genotyped for 7 SNPs within MMP2, MMP9 and TIMP2 genes, along with the assessment of semen parameters (concentration, motility and morphology of spermatozoa). No association was observed between the studied genotypes and male infertility. However, higher sperm concentration was associated with TIMP2 rs8080623 C and rs2277698 T variants among infertile men, and with MMP9 rs17576 A minor allele in controls (p < .05). TIMP2 rs9900972 T and rs2277698 T allele were associated with higher percentage of morphologically normal spermatozoa among controls. MMP2 rs2285053 TT homozygous infertile patients presented higher percentage of spermatozoa displaying nonprogressive motility. Haplotype analysis revealed strong linkage disequilibrium between the studied loci (5 of 8 possible TIMP2 haplotypes, and 3 of 4 possible MMP2 and MMP9 were found). None of the haplotypes showed association with infertility. This study results suggest an association between MMP9 and TIMP2 SNPs with sperm parameters, but not infertility.     

Rs9303628 and rs2054847 of SLC6A4 are protective factors for the onset of lifelong premature ejaculation among the Chinese population

The purpose of this study was to investigate whether the polymorphisms of SLC6A4 gene affect the occurrence of lifelong premature ejaculation (LPE). In this case–control study, Agena MassARRAY was used to genotype SLC6A4 polymorphisms of 91 LPE patients and 362 controls. Then, genetic model and haplotype analysis were utilised to explore the correlation between SLC6A4 polymorphisms and LPE risk. The results showed that allele T, genotype T/T and C/T-T/T of rs9303628 were significantly correlated with a decreased risk of LPE in allele (p = .009), co-dominant (p = .025) and dominant (p = .014) model respectively. Allele T and genotype C/T-T/T of rs2054847 reduced the risk of LPE in co-dominant (p = .015) and dominant (p = .030) models respectively. Furthermore, there was a significant correlation between A_rs9303628C_rs2054847 haplotype and the decreased the risk of LPE (p = .010). In conclusion, this study firstly proved that the presence of rs9303628 and rs2054847 in SLC6A4 gene was a protective factor for the occurrence of LPE in the Chinese Han population.     

A functional polymorphism in MMP1 could influence osteomyelitis development

Osteomyelitis (OM) is a bone infection characterized by necrosis and new formation of bone. Because matrix metalloproteases (MMPs) play an important role in bone extracellular matrix remodeling, we investigated the role of some MMP polymorphisms in OM patients. A total of 118 OM patients and 300 blood donors were genotyped for the polymorphisms of MMP1 (?1607 1G/2G) and MMP13 (?77A/G). Levels of MMPs (?1, ?2, ?3, ?8, ‐9, ?10, and ?13) and tissue inhibitors of metaloproteases (TIMP‐1, ‐2, and ‐4) in serum and in human osteoblasts obtained from OM biopsies also were determined. The MMP1 (–1607 2G/2G) genotype was significantly more frequent among OM patients compared with controls [65.3% versus 33.7%, χ² = 26.85, odds ratio (OR) = 3.24, 95% confidence interval (CI) 2.03–5.2, p < .0001]. The MMP1 2G allele also was more frequent in OM patients (73.3% versus 57.2%, χ² = 37.76, OR = 2.75, 95% CI 1.96–3.85, p < .0001). Carriers of the 2G allele had significantly higher osteoblast MMP1 mRNA and MMP‐1 serum levels than noncarriers (p < .04). Interleukin 1α (IL‐1α) increased MMP‐1 and ‐13 protein secretion and Ets1 mRNA expression by OM patients' osteoblasts. No association of the MMP13 (–77 A/G) polymorphism with OM was observed. The MMP1 (–1607 1G/2G) polymorphism might contribute to OM pathogenesis. This could be due to increased expression of MMP‐1 by osteoblasts and is regulated by IL‐1α. © 2010 American Society for Bone and Mineral Research     

Candidate gene approach identifies six SNPs in tenascin‐C (TNC) associated with degenerative rotator cuff tears

Evidence for a heritable predisposition to rotator cuff tears (RCTs) is growing. Unrelated Caucasian individuals with surgically diagnosed full thickness RCTs (cases) and elderly Caucasian controls with intact rotator cuffs were screened for differences at the candidate genes: TNC, Col5A1, TIMP‐1, MMP‐1, MMP‐2, MMP‐3, MMP‐9, and MMP‐13. A first cohort (59 cases; 32 controls) was genotyped with the Sequenom MassARRAY iPLEX system. Of 142 SNPs within about 67–kbp of the TNC gene, 30 were tested for differences in proportions between cases and controls. A second, matched cohort (96 patients; 44 controls) was also genotyped for the same 30 SNPs, but with the KASP™ genotyping technology. Combining the two cohorts and after Bonferroni correction, six SNPs were significantly associated with RCT. Compared to controls, RCT patients showed a significantly higher rate of homozygosity at rs72758637, rs7021589, and rs1138545; a significantly higher rate of heterozygosity at rs10759753, rs3789870, and rs7035322 and a higher minor allele frequency at rs3789870. Rs1138545, a missense SNP in exon10 might be of biological significance because it varies the amino acid sequence close to the TNC‐FNIII5 domain. The FNIII5 domain binds multiple growth factors and co‐ligates with integrins during tendon healing. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:894–901, 2017.

     

An analysis of the association between the vitamin D pathway and serum 25‐hydroxyvitamin D levels in a healthy Chinese population

Vitamin D deficiency has been recognized as a major public health issue worldwide. Recent studies have indicated that genetic factors might play an important role in determining serum 25‐hydroxyvitamin D [25(OH)D] levels in Caucasians and African Americans. However, the genes that contribute to the variation in serum 25(OH)D levels in Chinese are unknown. In this study, we screened 15 key genes within the vitamin D metabolic pathway using 96 single‐nucleotide polymorphism (SNP) markers in a group of 2897 unrelated healthy Chinese subjects. Significant confounding factors that may influence the variability in serum 25(OH)D levels were used as covariates for association analyses. An association test for quantitative traits was performed to evaluate the association between candidate genes and serum 25(OH)D levels. In the present study, variants and/or haplotypes in GC, CYP2R1, and DHCR7/NADSYN1 were identified as being associated with 25(OH)D levels. Participants with three or four risk alleles of the two variants (GC‐rs4588 and CYP2R1‐rs10766197) had an increased chance of presenting with a 25(OH)D concentration lower than 20 ng/mL (odds ratio 2.121, 95% confidence interval 1.586–2.836, p = 6.1 × 10^?8) compared with those lacking the risk alleles. Each additional copy of a risk allele was significantly associated with a 0.12‐fold decrease in the log‐25(OH)D concentration (p = 3.7 × 10^?12). Haplotype TGA of GC rs705117‐rs2282679‐rs1491710, haplotype GAGTAC of GC rs842999‐rs705120‐rs222040‐rs4588‐rs7041‐rs10488854, haplotype CA of GC rs1155563‐rs222029, and haplotype AAGA of CYP2R1 rs7936142‐rs12794714‐rs2060793‐rs16930609 were genetic risk factors toward a lower 25(OH)D concentration. In contrast, haplotype TGGGCCC of DHCR7/NADSYN1 rs1790349‐rs7122671‐rs1790329‐rs11606033‐rs2276360‐rs1629220‐rs2282618 were genetic protective factors. The results suggest that the GC, CYP2R1, and DHCR7/NADSYN1 genes might contribute to variability in the serum 25(OH)D levels in a healthy Chinese population in Shanghai. These markers could be used as tools in Mendelian randomization analyses of vitamin D, and they could potentially be drug targets in the Chinese population in Shanghai.     

A Haplotype‐Based Analysis of the LRP5 Gene in Relation to Osteoporosis Phenotypes in Spanish Postmenopausal Women

LRP5 encodes the low‐density lipoprotein receptor‐related protein 5, a transmembrane protein involved in Wnt signaling. LRP5 is an important regulator of osteoblast growth and differentiation, affecting bone mass in vertebrates. Whether common variations in LRP5 are associated with normal BMD variation or osteoporotic phenotypes is of great relevance. We used a haplotype‐based approach to search for common disease‐associated variants in LRP5 in a cohort of 964 Spanish postmenopausal women. Twenty‐four SNPs were selected, covering the LRP5 region, including the missense changes p.V667M and p.A1330V. The SNPs were genotyped and evaluated for association with BMD at the lumbar spine (LS) or femoral neck (FN) and with osteoporotic fracture, at single SNP and haplotype levels, by regression methods. Association with LS BMD was found for SNP 1, rs312009, located in the 5′‐flanking region (p = 0.011, recessive model). SNP 6, rs2508836, in intron 1, was also associated with BMD, both at LS (p = 0.025, additive model) and FN (p = 0.031, recessive model). Two polymorphisms were associated with fracture: SNP 11, rs729635, in intron 1, and SNP 15, rs643892, in intron 5 (p = 0.007 additive model and p = 0.019 recessive model, respectively). Haplotype analyses did not provide additional information, except for haplotype “GC” of the block located at the 3′end of the gene. This haplotype spans intron 22 and the 3′ untranslated region and was associated with FN BMD (p = 0.029, one copy of the haplotype versus none). In silico analyses showed that SNP 1 (rs312009) lies in a putative RUNX2 binding site. Electro‐mobility shift assays confirmed RUNX2 binding to this site.     

Single nucleotide polymorphisms in Renalase and KCNQ1 genes and female infertility: A cross‐sectional study in Pakistan

A global increase in the incidence of subfertility is observed, and research suggests strong genetic influences that might restrict fertility directly or indirectly. It therefore becomes important to rule out the existence of genetic causes and counsel infertile couples before offering “Advanced Infertility Treatment Techniques.” This cross‐sectional study aimed to explore the association of KCNQ1 (rs2237895) and Renalase (rs2576178 and rs10887800) single nucleotide polymorphisms with different causes of infertility by analysing 508 fertile and 164 infertile women. Gene variant (AC/CC) of KCNQ1 rs2237895 showed a slight difference in the endometriosis group compared to the fertile group (p = .049), with the C allele showing a significant association with infertility overall (OR = 1.42 [1.100–1.833]; p < .0069). The variant AG/GG of Renalase rs2576178 was significantly associated with overall infertility (OR = 2.266; p < .001), with a strong G allele association with unexplained infertility OR = 2.796 (p = .002) that remained significant after adjusting for age and body mass index. Similarly, Renalase rs10887800 AG/GG and G allele showed significant association with both infertility due to polycystic ovarian syndrome and unexplained infertility. Expression of single nucleotide polymorphism rs2237895 and rs2576178 in both KCNQ1 and Renalase genes might be responsible for altering reproductive potential, hence leading to infertility in women.     

The Apoptosis Pathway and CASP8 Variants Conferring Risk for Acute and Overuse Musculoskeletal Injuries

Rotator cuff tendinopathy (RCT), anterior cruciate ligament (ACL) ruptures, and carpal tunnel syndrome (CTS), are examples of chronic (RCT and CTS) and acute (ACL ruptures) musculoskeletal soft tissue injuries. These injuries are multifactorial in nature, with several identified intrinsic and extrinsic risk factors. Previous studies have implicated specific sequence variants within genes encoding structural and regulatory components of the extracellular matrix of tendons and/ligaments to predispose individuals to these injuries. An example, includes the association of sequence variants within the apoptotic regulatory gene, caspase-8 (CASP8) with other musculoskeletal injury phenotypes, such as Achilles tendinopathy. The primary aim of this study was, therefore, to investigate previously implicated DNA sequence variants within CASP8: rs3834129 (ins/del) and rs1045485 (G/C), and the rs13113 (T/A) identified using a whole exome sequencing approach, with risk of musculoskeletal injury phenotypes (RCT, ACL ruptures, and CTS) in three independent studies. In addition, the aim was to implicate a CASP8 genomic interval in the modulation of risk of RCT, ACL ruptures, or CTS. It was found that the AA genotype of CASP8 rs13113 (T/A) was independently associated with increased risk for CTS. In addition, it was found that the del-C haplotype (rs3834129–rs1045485) was significantly associated with non-contact ACL ruptures, which is in alignment with previous research findings. Collectively, the results of this study implicate the apoptosis pathway as biologically significant in the underlying pathogenesis of musculoskeletal injury phenotypes. These findings should be repeated in larger sample cohorts and across different populations. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:680–688, 2020     

The -1997 G/T and Sp1 Polymorphisms in the Collagen Type I alpha1 (<Emphasis Type="Italic">COLIA1</Emphasis>) Gene in Relation to Changes in Femoral Neck Bone Mineral Density and the Risk of Fracture in the Elderly: The Rotterdam Study

The COLIA1 Sp1 polymorphism has been associated with bone mineral density (BMD) and fracture. A promoter polymorphism, -1997 G/T, also has been associated with BMD. In this study, we examined whether these polymorphisms alone and in the form of haplotypes influence bone parameters and fracture risk in a large population-based cohort of elderly Caucasians. We determined the COLIA1 -1997 G/T (promoter) and Sp1 G/T (intron) polymorphisms in 6,280 individuals and inferred haplotypes. Femoral neck BMD and BMD change were compared across COLIA1 genotypes at baseline and follow-up (mean 6.5 years). We also investigated the relationship between the COLIA1 polymorphisms and incident nonvertebral fractures, which were recorded during a mean follow-up period of 7.4 years. Vertebral fractures were assessed by radiographs on 3,456 genotyped individuals. Femoral neck BMD measured at baseline was 3.8% lower in women carrying two copies of the T-Sp1 allele (P for trend = 0.03). No genotype dependent differences in BMD loss were observed. In women homozygous for the T allele of the Sp1 polymorphism, the risk of fragility fracture increased 2.3 times (95% confidence interval 1.4–3.9, P = 0.001). No such association was observed with the promoter polymorphism. In men, no association with either the Sp1 or the -1997 G/T promoter polymorphism was seen with BMD or fracture. High linkage disequilibrium (LD; D′ = 0.99, r ² = 0.03) exists between the two studied polymorphisms. We observed three haplotypes in our population: haplotype 1 (G_promoter–G_intron) frequency (f) = 69%, haplotype 2 (G_promoter–T_intron) f = 17.6%, and haplotype 3 (T_promoter–G_intron) f = 13.4%. Haplotype 2 was associated with a 2.1-fold increased risk of fragility fracture in women (95% confidence interval 1.2–3.7, P = 0.001). We confirm that the COLIA1 Sp1 polymorphism influences BMD and the risk of fracture in postmenopausal Caucasian women. In contrast, we found no independent effect of the -1997 G/T promoter polymorphism on BMD or fracture.     

A Rare Haplotype in the Upstream Regulatory Region of COL1A1 Is Associated With Reduced Bone Quality and Hip Fracture

Three polymorphisms have been identified in the 5′ regulatory region of the COL1A1 gene at positions −1997 (rs1107946), −1663 (rs2412298), and +1245G/T (rs1800012), which combine to form haplotypes that have been associated with BMD in several populations. These polymorphisms and haplotypes have not thus far been studied in relation to biomechanical properties of bone or fracture risk. Genotypes and haplotypes of the COL1A1 gene were related to the biomechanical properties of bone ex vivo in samples of bone tissue obtained from the femoral head of 98 consecutive patients undergoing surgery for low-trauma hip fractures. Genotype and haplotype frequencies in the hip fracture cases were compared with 3418 population-based controls recruited from the same region. All three polymorphisms were associated with material density of the bone core, yield strength, and toughness. The association between −1663InsdelT and +1245G/T alleles, yield strength, and toughness remained significant after adjusting for material density of the core and other confounding factors. A haplotype comprising the unfavorable allele at all three polymorphic sites (−1997T/−1663delT/+1245T) was also associated with yield strength, modulus, and toughness after adjusting for confounding factors. This haplotype was carried by 19/94 (20.2%) patients with hip fracture compared with only 2/3399 (0.06%) female controls drawn from the general population (p < 0.0001). In contrast, there was no significant difference between cases and controls in genotype distribution for the individual polymorphisms. This study shows that common genetic variants in the 5′ regulatory region of COL1A1 are associated with biomechanical properties of bone and reduced bone quality by mechanisms independent of their effects on BMD. The biomechanically unfavorable allele at each polymorphic site defines a haplotype that is extremely rare in the general population but that is ∼400-fold enriched in hip fracture patients. This haplotype may have clinical value as a genetic marker for susceptibility to hip fracture, and further studies to investigate this possibility would be of interest.     

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

The aim of this study was to determine if single‐nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r² ≥ 0.8) were selected for RANKL, RANK, and OPG and their 10‐kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome‐wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population‐based study of male aging, the European Male Ageing Study (EMAS). N‐terminal propeptide of type I procollagen (PINP) and C‐terminal cross‐linked telopeptide of type I collagen (CTX‐I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total‐hip areal BMD (BMD_a) was measured by dual‐energy X‐ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (β = 1.83, p = .004) and CTX‐I (β = 17.59, p = 4.74 × 10^?4), and lower lumbar spine BMD_a (β = ?0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (β = ?1.84, p = .003) and CTX‐I (β = ?27.02, p = 6.06 × 10^?8) and higher ultrasound BMD at the calcaneus (β = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. © 2010 American Society for Bone and Mineral Research     

Association of MMP‐1 ‐1607 1G/2G (rs1799750) polymorphism with primary knee osteoarthritis in the Greek population

Osteoarthritis is the most common form of arthritis with still unknown pathogenic etiology and considerable contribution of genetic factors. One of the mechanisms of cartilage degradation in osteoarthritis is enzymatic proteolysis of the extracellular matrix by metalloproteinases. MMP‐1, produced by chondrocytes and synovial cells, is a major proteinase of the MMPs family. The present study aims at evaluating the association of MMP1 gene ‐1607 1G/2G (rs1799750) polymorphism with primary knee osteoarthritis in the Greek population. One hundred fifty five patients with primary symptomatic knee osteoarthritis participated in the study along with 139 controls. Genotypes were determined using PCR—RLFP technique. Allelic and genotypic frequencies were compared between both study groups. There was no significant association between MMP1 ‐1607 1G/2G polymorphism and knee osteoarthritis, in crude analysis; however, after multiple logistic regression analysis, 1G/2G was associated with reduced odds of knee osteoarthritis by 75% in males, compared to genotypes 1G/1G + 2G/2G, adjusting for age and BMI (adjusted OR: 0.25, 95% CI: 0.069, 0.910, p = 0.035). The present study shows that MMP1 ‐1607 1G/2G (rs1799750) polymorphism might be a risk factor for knee osteoarthritis susceptibility in the Greek population. Further investigations are needed to confirm this association in the pathogenesis of osteoarthritis. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1155–1160, 2014.

     

Chemerin rs17173608 and vaspin rs2236242 gene variants on the risk of end stage renal disease (ESRD) and correlation with plasma malondialdehyde (MDA) level

Introduction: End-stage renal disease (ESRD) is associated with critical kidney illness that seriously affects the lifespan. Genetic factors and oxidative stress could play critical role in the development of ESRD. We assessed the association between chemerin rs17173608 T/G and vaspin rs2236242 T/A genes variants with the risk of ESRD and their correlation with plasma malondialdehyde (MDA) level.

Materials and methods: In a case-control study, 131 gender and age-matched unrelated healthy controls and 110 ESRD patients were enrolled. The chemerin rs17173608 T/G and vaspin rs2236242 T/A were detected by Tetra primer-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). The MDA concentration was determined by HPLC.

Results: Our findings for the first time revealed that in codominant genetic model (T/G vs. T/T genotype), the T/G genotype of chemerin gene significantly had a protective role against ESRD susceptibility. Also, in the presence of chemerin G allele, the risk of ESRD decreased by 0.79-fold (p?=?.048) in Kurdish population of Iran. The MDA serum levels in ESRD patients carrying the chemerin T/G?+?G/G genotype of rs17173608 T/G and also in carriers of A/A?+?T/A genotype of vaspin rs2236242 T/A were significantly higher compared to those in control subjects. The overall distribution of vaspin rs2236242 T/A genotypes and alleles comparing ESRD patients and healthy subjects were not statistically significant.

Conclusion: We found that the G allele of chemerin rs17173608 compared to T allele decreased the risk of ESRD, and there was a significant association between chemerin and vaspin variants with plasma MDA level in a sample of the Iranian population.     

Multiple sites of vascular dilation or aneurysmal disease and matrix metalloproteinase genetic variants in patients with abdominal aortic aneurysm

Objective

The objective of this study was to assess whether functional genetic polymorphisms of matrix metalloproteinases (MMPs) 1, 3, 9, and 12 are associated with arterial enlargements or aneurysms of the thoracic aorta or popliteal arteries in patients with abdominal aortic aneurysm (AAA).

Polymorphisms in BMP4 and FGFR1 genes are associated with fracture non‐union

Fracture healing is a complex process influenced by a multitude of factors and expression of several thousand genes. Polymorphisms in these genes can lead to an extended healing process and explain why certain patients are more susceptible to develop non‐union. A total of 16 SNPs within five genes involved in bone repair pathogenesis (FAM5C, BMP4, FGF3, FGF10, and FGFR1) were investigated in 167 patients with long bone fractures, 101 with uneventful healing, and 66 presenting aseptic non‐unions. Exclusion criteria were patients presenting pathological fractures, osteoporosis, hypertrophic and infected non‐unions, pregnancy, and children. All genetic markers were genotyped using TaqMan real‐time PCR. Chi‐square test was used to compare genotypes, allele frequencies, and haplotype differences between groups. Binary logistic regression analyzed the significance of many covariates and the incidence of non‐union. Statistical analysis revealed open fracture to be a risk factor for non‐union development (p < 0.001, OR 3.6 [1.70–7.67]). A significant association of haplotype GTAA in BMP4 (p = 0.01) and FGFR1 rs13317 (p = 0.005) with NU could be observed. Also, uneventful healing showed association with FAM5C rs1342913 (p = 0.04). Our work supported the role of BMP4 and FGFR1 in NU fracture independently of the presence of previously described risk factors. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1971–1979, 2013     

Muscle strength is associated with vitamin D receptor gene variants

Vitamin D receptor (VDR) is an important candidate gene in muscle function. Scientific reports on the effect of its genetic variants on muscle strength are contradictory likely due to the inconsistent study designs. Hand grip strength (HGS) is a highly heritable phenotype of muscle strength but only limited studies are available on its genetic background. Association between VDR polymorphisms and HGS has been poorly investigated and previous reports are conflicting. We studied the effect of VDR gene variants on HGS in a sample of 706 schoolchildren. Genomic DNA was extracted from saliva samples and six candidate single nucleotide polymorphisms (SNPs) across the VDR gene were genotyped with Sequenom MassARRAY technique. HGS was measured with a digital dynamometer in both hands. Single marker and haplotype associations were adjusted for demographic parameters. Three SNPs, rs4516035 (A1012G; p = 0.009), rs1544410 (BsmI; p = 0.010), and rs731236 (TaqI; p = 0.038) and a 3′ UTR haploblock constructed by three SNPs (Bsml‐Taq1‐rs10783215; p < 0.005) showed significantly associations with HGS of the dominant hand. In the non‐dominant hand, the effects of the A1012G (p = 0.034) and the 3′ UTR haploblock (p < 0.01) on HGS were also significant. Since the promoter SNP (A10112G) and the 3′ UTR haplotype were proved to be associated with the expression and the stability of the VDR mRNA in earlier studies, VDR variants can be supposed to have a direct effect on muscle strength. The individual genetic patterns can also explain the inconsistency of the previously published clinical results on the association between vitamin D and muscle function. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2031–2037, 2016.     

Nuclear Factor Erythroid-2-related Factor 2 Gene Polymorphisms in Vitiligo

BackgroundOxidative stress is now one of the accepted theories of vitiligo development. Nuclear factor erythroid-2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins.ObjectiveThis work aimed to evaluate the association of Nrf2 gene polymorphisms with the susceptibility to vitiligo among a sample of Egyptian patients with vitiligo.MethodsThis case-control study included 100 patients with vitiligo and 50 healthy matched volunteers serving as a control group. Genotyping was carried out by real-time polymerase chain reaction.ResultsThe frequencies of TT, CT, and combined (TT+CT) genotypes and the T allele of Nrf2 (rs35652124) were significantly increased in the studied patients with vitiligo relative to the healthy controls (p<0.001, p=0.012, p<0.001 and p<0.001, respectively). There was a nonsignificant difference between patients and controls regarding Nrf2 (rs6721961) genotypes. However, the T allele of Nrf2 (rs6721961) was significantly predominant in the studied patients compared to in the controls (p=0.029). Among the studied criteria, the T allele of Nrf2 (rs6721961) was predominant in patients with a marginal type of repigmentation (p=0.022), while the G allele of the same single-nucleotide polymorphism was associated with a higher body mass index value (p=0.034). One hundred percent of patients with vitiligo with the Nrf2 (rs6721961) GT genotype had a progressive disease course (p=0.015).ConclusionNrf2 (−617 T/G) and (−653 T/C) polymorphism might play a role in patient susceptibility to vitiligo and modify the clinical presentation of the disease.     

Effect of IL-6 C-572G polymorphism on idiopathic membranous nephropathy risk in a han chinese population

Membranous glomerulonephritis (MGN) is viewed as an immune-mediated glomerular disease, with immunologic expression occurring in genetically susceptible persons. The cytokine interleukin-6 (IL-6) gene polymorphism is known to impair intracellular signaling pathways following adaptive immune response. Our study gauged the effects of IL-6 C-572G (rs1800796) single nucleotide polymorphism (SNP) on MGN among Taiwan's Han Chinese population, as analyzed in 265 controls and 106 MGN patients. Genotyping for IL-6 C-572G SNP was performed by restriction fragment length polymorphism assay. Data showed stark differences in genotype and allele frequency distributions at IL-6 C-572G SNP between MGN patients and controls (p = 1.6E-04 and 1.7E-04, respectively). People with C allele or with CC genotype at IL-6 C-572G SNP showed higher risk of MGN (odds ratio = 2.42 and 2.71, respectively; 95% confidence interval = 1.51–3.87 and 1.60–4.60, respectively). These point to IL-6 C-572G polymorphism as the underlying cause of MGN; polymorphism merits further investigation.     

高频超声与MRI诊断肩袖撕裂

目的 对比高频超声与MRI诊断创伤性与非创伤性肩袖撕裂(RCT)的效能。方法 纳入59例接受关节镜手术的创伤性(创伤组,n=35)与非创伤性(非创伤组,n=24)肩部疼痛和/或功能障碍患者,以关节镜所见为金标准,比较高频超声与MRI术前诊断RCT的效能,以及高频超声诊断符合率的组间差异。结果 关节镜诊断RCT 42例(42/59,71.19%),包括创伤组25例、非创伤组17例,均存在冈上肌腱撕裂;其中26例冈上肌腱全层撕裂、16例部分撕裂。高频超声与MRI诊断冈上肌腱全层撕裂(92.31%vs. 96.15%)与部分撕裂(62.50%vs. 75.00%)的准确率差异均无统计学意义(P均>0.05);组内二者诊断RCT效能差异均无统计学意义(P均>0.05)。高频超声(85.71%vs. 54.17%)及MRI(91.43%vs. 62.50%)诊断创伤组RCT符合率均大于非创伤组(P均<0.01);2组组内高频超声、MRI诊断符合率差异均无统计学意义(P均>0.05)。结论 高频超声诊断RCT效能与MRI相当。