A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5′ UTR of GDF5 with osteoarthritis susceptibility
A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5′ UTR of GDF5 with osteoarthritis susceptibility
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DOI：
10.1093/hmg/ddn038
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发表时间：
2008-05-15
影响因子：
3.5
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
--
作者：
Chapman, Kay;Takahashi, Atsushi;Ikegawa, Shiro
我们对超过11，000人的数据进行了荟萃分析。它提供了令人信服的证据，证明欧洲和亚洲人群中GDF 5（+104 T/C; rs 143383）5 '-UTR中的功能性单核苷酸多态性（SNP）与骨关节炎（OA）之间存在正相关性。该SNP最近被报道与日本和中国汉族人群中的OA相关。在欧洲样本中复制这种关联的尝试是不确定的，因为当单独研究时，在英国，西班牙和希腊的病例对照队列中没有发现关联。然而，英国和西班牙的汇总数据发现T等位基因与比值比（OR）为1.10相关。尽管欧洲研究有足够的能力复制日本队列的原始结果（OR = 1.79），但这些结果表明GDF 5多态性在欧洲人中的作用可能不那么强。为了澄清欧洲的研究是否受到力量不足的阻碍，我们将来自英国和荷兰的新数据与欧洲和亚洲的三项已发表研究相结合。这些结果为GDF 5 SNP与欧洲人和亚洲人的膝关节OA呈正相关提供了强有力的证据。等位基因频率模型（P = 0.0004，OR = 1.21）和显性模型（P < 0.0001，OR = 1.48）显示两个种族组的联合关联非常显著。这些发现代表了第一个高度重要的证据，表明OA的发展是一个危险因素，影响两个高度不同的种族群体。
We have performed a meta-analysis combining data for more than 11,000 individuals. It provides compelling evidence for a positive association between a functional single-nucleotide polymorphism (SNP) in the 5'-UTR of GDF5 (+104T/C; rs143383) and osteoarthritis (OA) in European and Asian populations. This SNP has recently been reported to be associated with OA in Japanese and Han Chinese populations. Attempts to replicate this association in European samples have been inconclusive, as no association was found in the case-control cohorts from the UK, Spain and Greece when studied individually. However, the pooled data of UK and Spain found an association of the T-allele with an odds ratio (OR) of 1.10. Although the European studies had adequate power to replicate the original findings from the Japanese cohort (OR = 1.79), these results suggest that the role of the GDF5 polymorphism may not be as strong in Europeans. To clarify whether the European studies were hampered by insufficient power, we combined new data from the UK and the Netherlands with the three published studies of Europe and Asia. The results provide strong evidence of a positive association of the GDF5 SNP with knee OA for Europeans as well as for Asians. The combined association for both ethnic groups is highly significant for the allele frequency model (P = 0.0004, OR = 1.21) and the dominant model (P < 0.0001, OR = 1.48). These findings represent the first highly significant evidence for a risk factor for the development of OA which affects two highly diverse ethnic groups.