Strong association of the polymorphisms in PBEF1 and knee OA risk: a two-stage population-based study in China.
Strong association of the polymorphisms in PBEF1 and knee OA risk: a two-stage population-based study in China.
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DOI：
10.1038/srep19094
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发表时间：
2016-01-11
影响因子：
4.6
通讯作者：
Jiang L
中科院分区：
文献类型：
--
作者：
Chu M;Rong J;Wang Y;Zhu L;Xing B;Tao Y;Zhuang X;Zhao Y;Jiang L
前B细胞集落增强因子1（PBEF 1）与肥胖的相关性及其促炎特性表明，PBEF 1可能是将炎症与肥胖和原发性骨关节炎（OA）联系起来的另一个关键介质。我们假设PBEF 1的多态性可能改变OA的发生风险。因此，我们系统地筛选了PBEF 1的4个标签多态性（rs4730153，rs2058540，rs3801267和rs16872158），并在两阶段病例对照研究中评估了遗传变异与OA风险之间的关联，第一阶段包括196例病例和442名对照，第二阶段包括143例病例和238名对照。在第一阶段中，发现两个SNP（rs4730153和rs16872158）与OA风险潜在相关（P < 0.05），这在第二阶段中得到进一步证实，具有相似的效果。将这两个阶段合并后，我们发现rs4730153在加性遗传模型中与OA风险降低显著相关（P < 0.05），而rs16872158显示OA风险增加（P < 0.05）。这2个SNP的联合分析显示，风险等位基因数量与OA风险之间存在显著的等位基因剂量相关性（P趋势= 5.25 × 10−5）。这些结果表明PBEF 1基因的遗传变异可能改变了中国人群中OA的个体易感性。
The association of Pre-B cell colony enhancing factor 1 (PBEF1) with obesity, together with its pro-inflammatory properties suggests that PBEF1 might be another crucial mediator that links inflammation with obesity and primary osteoarthritis (OA). We hypothesized that polymorphisms in PBEF1 may modify the risk of developing OA. Thus we systematically screened 4 tagging polymorphisms (rs4730153, rs2058540, rs3801267 and rs16872158) in PBEF1 and evaluated the association between the genetic variants and OA risk in a two-stage case-control study including 196 cases and 442 controls in the first stage and 143 cases and 238 controls in the second stage. In the first stage, two SNPs (rs4730153 and rs16872158) were found to be potentially associated with OA risk (P < 0.05), which were further confirmed in the second stage with similar effects. After combining the two stages, we found that rs4730153 was significantly associated with decreased risk of OA in an additive genetic model (P < 0.05), while rs16872158 showed increased risk of developing OA (P < 0.05). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and OA risk (Ptrend = 5.25 × 10−5). These findings indicate that genetic variants in PBEF1 gene may modify individual susceptibility to OA in the Chinese population.