The rs4238326 polymorphism in ALDH1A2 gene potentially associated with non-post traumatic knee osteoarthritis susceptibility: a two-stage population-based study

Objective: A recent genome-wide association study reported significant associations of genetic variants within the ALDH1A2 gene with osteoarthritis (OA) of the hand in European populations. However, these findings have not been well generalized to other joints, or to other populations.Methods: We performed a two-stage population-based caseecontrol study including 196 non-post traumatic knee OA cases and 442 controls in the first stage and independent 143 non-post traumatic knee OA cases and 238 controls in the second stage in a Chinese population by genotyping eight tagging polymorphisms in ALDH1A2.Results: In the first stage, the single nucleotide polymorphism (SNP) rs4238326 was found to be potentially associated with knee OA risk (additive model: odds ratio [OR] = 0.70; 95% confidence interval [95% CI] = 0.49-1.01; P = 0.055), which was further confirmed in the second stage with similar effect (additive model: OR = 0.60; 95% CI = 0.38-0.95; P = 0.029). After combining the two stages, we found that the variant C allele of rs4238326 was probably associated with decreased risk of knee OA (additive model: OR = 0.65; 95% CI = 0.49-0.86; P = 0.003). Furthermore, interaction analyses showed that rs4238326 interacted multiplicatively with age to contribute to knee OA risk (interaction P = 0.041).Conclusions: These findings indicate that the SNP rs4238326 in ALDH1A2 gene may potentially modify individual susceptibility to knee OA in the Chinese population. Beyond that, further studies are warranted to validate and extend our findings, and future functional studies are required to clarify the possible mechanisms. (C) 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

目的：近期一项全基因组关联研究报告称，在欧洲人群中，ALDH1A2基因内的遗传变异与手部骨关节炎（OA）显著相关。然而，这些发现尚未很好地推广到其他关节或其他人群。 方法：我们在中国人群中进行了一项两阶段基于人群的病例对照研究，第一阶段包括196例非创伤后膝关节OA病例和442例对照，第二阶段包括独立的143例非创伤后膝关节OA病例和238例对照，对ALDH1A2中的8个标签多态性进行基因分型。 结果：在第一阶段，发现单核苷酸多态性（SNP）rs4238326可能与膝关节OA风险相关（加性模型：比值比[OR]=0.70；95%置信区间[95%CI]=0.49 - 1.01；P = 0.055），在第二阶段得到进一步证实，且效应相似（加性模型：OR = 0.60；95%CI = 0.38 - 0.95；P = 0.029）。将两个阶段合并后，我们发现rs4238326的变异C等位基因可能与膝关节OA风险降低相关（加性模型：OR = 0.65；95%CI = 0.49 - 0.86；P = 0.003）。此外，交互作用分析表明，rs4238326与年龄存在相乘交互作用，从而影响膝关节OA风险（交互作用P = 0.041）。 结论：这些发现表明，ALDH1A2基因中的SNP rs4238326可能潜在地改变中国人群对膝关节OA的个体易感性。除此之外，有必要进行进一步研究以验证和扩展我们的发现，并且需要未来的功能研究来阐明可能的机制。（C）2017由爱思唯尔有限公司代表国际骨关节炎研究协会出版。