Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
BMC Med Genet. 2010 Nov 16;11:164. doi: 10.1186/1471-2350-11-164.
The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis.
In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls.
The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (α = 0.05).
This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase.
本研究旨在探讨 ESR2 基因常见遗传变异与骨关节炎之间的关系。
在发现研究中，即鹿特丹研究 I 中，对 7 个单核苷酸多态性（SNP）进行基因分型，并采用加性模型对其与髋关节（284 例病例，2772 例对照）、膝关节（665 例病例，2075 例对照）和手部 OA（874 例病例，2184 例对照）的相关性进行检测。在复制阶段，对另外的 2080 例髋关节、1318 例膝关节和 557 例手部 OA 病例以及 4001 例、2631 例和 1699 例对照组，分别检测了一个 SNP（rs1256031）。对包含 2364 例髋关节、1983 例膝关节和 1431 例手部 OA 病例以及大约 6000 例对照组的完整数据集，采用固定效应和随机效应荟萃分析进行分析。
在鹿特丹研究 I 中，女性 rs1256031 的 C 等位基因与髋关节 OA 的患病风险增加 36%相关（OR 1.36，95%CI 1.08-1.70，p = 0.009）。单体型分析和膝关节及手部 OA 分析没有提供额外信息。在复制研究中，荟萃分析并未显示该 SNP 对全人群髋关节 OA 的显著影响（OR 1.06，95%CI 0.99-1.15，p = 0.10）。按性别分层并未改变结果。在本研究中，我们有 80%的效能来检测髋关节 OA 的优势比至少为 1.14（α = 0.05）。
本研究表明，ESR2 基因的常见遗传变异不太可能影响骨关节炎的风险，其影响小于 13%的增加。
