Rare variant of MAP2K7 is associated with increased risk of COPD in southern and eastern Chinese
Rare variant of MAP2K7 is associated with increased risk of COPD in southern and eastern Chinese
复制标题
MAP2K7 的罕见变异与中国南部和东部地区慢性阻塞性肺病 (COPD) 风险增加相关
DOI：
10.1111/resp.12976
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发表时间：
2017
期刊：
影响因子：
6.9
通讯作者：
Lu Jiachun
中科院分区：
文献类型：
--
作者：
Qiu Fuman;Li Yinyan;Lu Xiaoxiao;Xie Chenli;Nong Qingqing;Wu Di;Chen Jiansong;Yang Lei;Zhou Yifeng;Lu Jiachun
背景和目的广泛的常见基因座与各种复杂疾病的相关性已被广泛筛选和评估，然而，引起蛋白编码基因错义替换的罕见变异在人类疾病中的相关性仍不清楚。方法在本研究中，我们对中国南方和东部地区1791例COPD患者和1940名对照进行了两阶段的回顾性研究，以检验人类丝裂原激活蛋白激酶7(MAP2K7)的5个罕见变异(即p.Glu116Lys、p.Asn118Ser、p.Arg138Cys、p.Ala195Thr和p.Leu259Phe)与COPD易感性的相关性。结果P.Glu116Lys罕见变异与COPD风险显著相关。与谷氨酸/谷氨酸野生型相比，携带116Lys稀有变异(Lys/Glu+Lys/Lys)的个体患慢性阻塞性肺疾病的危险性增加(OR = 3.83，95%CI：2.64~5.56；P= 1.45 × 10−12)。同时，携带116Lys稀有变异(Lys/Glu+Lys/Lys)的携带者1 S用力呼气量低于Glu/Glu携带者(FEV1前：1.74 ± 0.70vs 2.00 ± 0.68；P= 3.97 × 10−5；P= 2.40 × 10−10)。结论MAP2K7基因的p.Glu116Lys罕见变异与其携带者易患COPD，为中国人COPD易感性提供了一个有用的遗传生物标志物。
Background and objectiveA wide range of common loci have been extensively screened and evaluated for their associations with various complex diseases; however, the relevance of rare variants causing missense substitutions in the protein‐coding genes in human diseases is still poorly understood.MethodsIn this study, we conducted a two‐stage retrospective study of a total of 1791 patients with COPD and 1940 controls in southern and eastern Chinese to test relevancies of five rare variants (i.e. p.Glu116Lys, p.Asn118Ser, p.Arg138Cys, p.Ala195Thr and p.Leu259Phe) of human mitogen‐activated protein kinase kinase 7 (MAP2K7) to COPD susceptibility. The effects of these loci on lung function were further estimated.ResultsThe p.Glu116Lys rare variant had significant associations with COPD risk. Compared to individuals with Glu/Glu wild‐genotype, those with 116Lys rare variants (Lys/Glu+Lys/Lys) had an increased risk of COPD (OR = 3.83, 95% CI: 2.64–5.56;P= 1.45 × 10−12). Meanwhile, the carriers with 116Lys rare variants (Lys/Glu+Lys/Lys) had lower pre‐forced expiratory volume in 1 s (pre‐FEV1: 1.74 ± 0.70 vs 2.00 ± 0.68;P= 3.97 × 10−5) and lower pre‐FEV1to pre‐forced vital capacity ratio (pre‐FEV1/FVC: 0.68 ± 0.14 vs 0.75 ± 0.12;P= 2.40 × 10−10) than those with Glu/Glu genotype. However, for other rare variants, no significant association with either COPD risk or lung function was observed.ConclusionOur data strongly suggest that the p.Glu116Lys rare variant inMAP2K7predisposes its carriers to develop COPD, which would provide a useful genetic biomarker for COPD susceptibility in Chinese.