Dataset Information

Association between genetic variants of DVWA and osteoarthritis of the knee and hip: a comprehensive meta-analysis.

ABSTRACT: Recently, double von Willebrand factor domain A (DVWA) gene, a previously unknown gene, was revealed to contain several single nucleotide polymorphisms (SNPs) that showed consistent association with knee osteoarthritis (OA) in Japanese and Chinese cohorts. However, subsequent studies failed to confirm this result in several different populations. To deal with the issues raised by inconsistent results among those studies, we investigated the association between DVWA and OA using meta-analytic techniques, combining all published data up to December 2014. 10 independent samples from 4 teams contributed data for a possible association between SNP rs7639618 and knee or hip OA. The total number of cases and controls of this SNP was respectively 4,142 versus 6,575 for knee OA, and 2,325 versus 2,914 for hip OA. A trend of significant association was observed in the combined population with knee OA (P=0.06), and a significant difference was identified between patients with knee OA and controls for the G-allele of rs7639618 (P=0.02). Together with the reported functional studies, our results indicate that DVWA may have a small but strong effect on the susceptibility to knee OA, at least in Asian population. Further functional studies are needed to determine the underlying variation of DVWA and to relate this to the pathophysiology of OA.

SUBMITTER: Zhang R

PROVIDER: S-EPMC4538189 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association between genetic variants of DVWA and osteoarthritis of the knee and hip: a comprehensive meta-analysis.

Zhang Rui R Yao Jianfeng J Xu Peng P Ji Baohu B Voegeli Géraldine G Hou Weikun W Li Hui H Wang Yi Y Kelsoe John R JR Ma Jie J

International journal of clinical and experimental medicine 20150615 6

Recently, double von Willebrand factor domain A (DVWA) gene, a previously unknown gene, was revealed to contain several single nucleotide polymorphisms (SNPs) that showed consistent association with knee osteoarthritis (OA) in Japanese and Chinese cohorts. However, subsequent studies failed to confirm this result in several different populations. To deal with the issues raised by inconsistent results among those studies, we investigated the association between DVWA and OA using meta-analytic tec ...[more]

PMID: 26309605

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Project description:OBJECTIVE:GDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large-scale meta-analysis of individual-level data. METHODS:Fourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex-specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed-effects and random-effects models for allele-based effects, and also for haplotype effects for FRZB. RESULTS:A significant random-effects summary OR for knee OA was demonstrated for rs143383 (1.15 [95% confidence interval 1.09-1.22]) (P=9.4x10(-7)), with no significant between-study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between-study heterogeneity was observed, and statistical significance was borderline (for OA of the hip [P=0.016]) or absent (for OA of the hand [P=0.19]). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P=0.019). CONCLUSION:Evidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different populations only for knee OA. Findings of this collaborative analysis do not support the notion that FRZB rs7775 or rs288326 has any sizable genetic effect on OA phenotypes.

Dataset Information

Association between genetic variants of DVWA and osteoarthritis of the knee and hip: a comprehensive meta-analysis.

Publications

Association between genetic variants of DVWA and osteoarthritis of the knee and hip: a comprehensive meta-analysis.

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