Meulenbelt Ingrid, Chapman Kay, Dieguez-Gonzalez Rebeca, Shi Dongquan, Tsezou Aspasia, Dai Jin, Malizos Konstantinos N, Kloppenburg Margreet, Carr Andrew, Nakajima Masahiro, van der Breggen Ruud, Lakenberg Nico, Gomez-Reino Juan J, Jiang Qing, Ikegawa Shiro, Gonzalez Antonio, Loughlin John, Slagboom Eline P
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Hum Mol Genet. 2009 Apr 15;18(8):1518-23. doi: 10.1093/hmg/ddp053. Epub 2009 Jan 30.
Recently, through a genome wide association study in Japanese knee osteoarthritis (OA) cases, a previously unknown gene, DVWA, was identified. The non-synonymous single nucleotide polymorphism (SNP) rs7639618 was subsequently found to be consistent and most significantly associated in Japanese and Han Chinese knee OA studies and functional relevant. Here, the association of the DVWA polymorphisms (rs7639618, rs11718863 and rs9864422) was genotyped in 1120 knee OA cases, 1482 hip OA cases and 2147 controls, all of white European descent from the Netherlands, the UK, Spain and Greece. Random effect DerSimonian and Laird meta-analyses were performed to assess the association in the different strata. To assess a more global effect, the original Japanese and Chinese data were included with the European. The meta-analyses provided evidence for global association of rs7639618 with knee OA with an odds ratio (OR) of 1.29, 95% confidence interval (CI) of 1.15-1.45 and a P-value of 2.70 x 10(-5). This effect, however, showed moderate heterogeneity, and rs7639618 was not independently associated with knee OA in Europeans, with an OR of 1.16, 95% CI of 0.99-1.35 and a P-value of 0.063. Furthermore, no association was observed with hip OA in Europeans, with a P-value of 0.851. Our results suggest that there may be global relevance for the DVWA SNP rs7639618 among knee OA cases, however, the apparent lower effect size in combination with the higher risk allele frequency in the European samples highlights again the ethnic differences in effects of discovered OA susceptibility genes.
最近,通过对日本膝关节骨关节炎(OA)病例进行全基因组关联研究,发现了一个此前未知的基因DVWA。随后发现非同义单核苷酸多态性(SNP)rs7639618在日本和汉族膝关节OA研究中具有一致性且关联最为显著,并且具有功能相关性。在此,对1120例膝关节OA病例、1482例髋关节OA病例和2147例对照进行了DVWA多态性(rs7639618、rs11718863和rs9864422)的基因分型,所有样本均为来自荷兰、英国、西班牙和希腊的白种欧洲人后裔。采用随机效应DerSimonian和Laird荟萃分析来评估不同分层中的关联。为了评估更全面的效应,将原始的日本和中国数据与欧洲数据合并。荟萃分析提供了rs7639618与膝关节OA全球关联的证据,优势比(OR)为1.29,95%置信区间(CI)为1.15 - 1.45,P值为2.70×10⁻⁵。然而,这种效应显示出中等程度的异质性,并且在欧洲人中rs7639618与膝关节OA无独立关联,OR为1.16,95%CI为0.99 - 1.35,P值为0.063。此外,在欧洲人中未观察到与髋关节OA的关联,P值为0.851。我们的结果表明,DVWA SNP rs7639618在膝关节OA病例中可能具有全球相关性,然而,欧洲样本中明显较低的效应量与较高风险等位基因频率再次凸显了已发现的OA易感基因效应的种族差异。