Kang Xi, Guo Ting, Liu Lyu, Ding Shui-Zi, Lei Cheng, Luo Hong
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China.
Chin Med J (Engl). 2020 Sep 5;133(17):2071-2077. doi: 10.1097/CM9.0000000000000858.
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Genome-wide association studies in non-Asian population revealed a link between COPD and mutations in the PTCH1 gene encoding Patched1, a receptor in the Hedgehog signaling pathway important for lung morphogenesis and pulmonary function. The aim of this study was to investigate the association between PTCH1 polymorphisms and the COPD risk in the Chinese Han population.
We performed a case-control study including 296 patients with COPD and 300 healthy individuals. Single-nucleotide polymorphisms in the PTCH1 gene were identified and genotyped based on the linkage disequilibrium analysis in all participants. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression analysis after adjustment for age, gender, and smoking.
In total, 28 single-nucleotide polymorphisms were identified in patients with COPD. Among them, "A" allele of rs28491365 (OR: 1.388, 95% CI: 1.055-1.827, P = 0.018), and "G" alleles of rs10512248 (OR: 1.299, 95% CI: 1.021-1.653, P = 0.033) and rs28705285 (OR: 1.359, 95% CI: 1.024-1.803, P = 0.033; respectively) were significantly associated with an increased COPD risk. Genetic model analysis revealed that the "T/T" genotype of rs34695652 was associated with a decreased COPD risk under the recessive model (OR: 0.490, 95% CI: 0.270-0.880, P = 0.010), whereas rs28504650/rs10512248 haplotype CG was significantly associated with an increased COPD risk after adjustment for age, gender, and smoking status (OR: 6.364, 95% CI: 1.220-33.292, P = 0.028).
The study provides a new insight into the role of PTCH1 polymorphisms in the susceptibility to COPD in the Chinese Han population.
慢性阻塞性肺疾病（COPD）是全球发病和死亡的主要原因。在非亚洲人群中进行的全基因组关联研究揭示了COPD与编码Patched1的PTCH1基因突变之间的联系，Patched1是刺猬信号通路中的一种受体，对肺形态发生和肺功能很重要。本研究的目的是调查PTCH1基因多态性与中国汉族人群COPD风险之间的关联。
我们进行了一项病例对照研究，包括296例COPD患者和300名健康个体。根据所有参与者的连锁不平衡分析，鉴定并对PTCH1基因中的单核苷酸多态性进行基因分型。在调整年龄、性别和吸烟因素后，使用逻辑回归分析估计比值比（OR）和95%置信区间（95%CI）。
COPD患者共鉴定出28个单核苷酸多态性。其中，rs28491365的“A”等位基因（OR：1.388，95%CI：1.055 - 1.827，P = 0.018），以及rs10512248（OR：1.299，95%CI：1.021 - 1.653，P = 0.033）和rs28705285（OR：1.359，95%CI：1.024 - 1.803，P = 0.033）的“G”等位基因分别与COPD风险增加显著相关。遗传模型分析显示，在隐性模型下，rs34695652的“T/T”基因型与COPD风险降低相关（OR：0.490，95%CI：0.270 - 0.880，P = 0.010），而rs28504650/rs10512248单倍型CG在调整年龄、性别和吸烟状态后与COPD风险增加显著相关（OR：6.364，95%CI：1.220 - 33.292，P = 0.028）。
该研究为PTCH1基因多态性在中国汉族人群COPD易感性中的作用提供了新的见解。
