中国人群慢性阻塞性肺疾病中 aquaporin5 基因的多态性

Polymorphisms of aquaporin5 gene in chronic obstructive pulmonary disease in a Chinese population.

作者信息

Ning Yunye, Ying Binwu, Han Suxia, Wang Baiding, Wang Xun, Wen Fuqiang

机构信息

Laboratory of Pulmonary Disease, State Key Laboratory of Biotherapy, West China Hospital, School of Life Science, Sichuan University, Chengdu, Sichuan, P. R. China.

出版信息

Swiss Med Wkly. 2008 Oct 4;138(39-40):573-8. doi: 10.4414/smw.2008.12240.

DOI:10.4414/smw.2008.12240

PMID:18853286

Abstract

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality. It is influenced by both environmental and genetic factors. Aquaporin5 plays a critical role in the maintenance of normal lung water homeostasis. We investigated whether polymorphisms in the gene aquaporin5 had any bearing on individual susceptibility to the development of COPD.

METHODS

332 COPD patients and 373 unrelated, age-matched healthy people were recruited for the study. All participants were Chinese Han people. We designed denaturing high performance liquid chromatography (DHPLC) to detect SNP in exons1, 2, 3 of AQP5 and DNA sequencing to confirm it. The allele +2254A>G (rs3736309) in intron3 and +3088A>G (Thr-Thr, rs41308104) in exon4 from NCBI dbSNP were genotyped by PCR-based restriction fragment length polymorphism.

RESULTS

We found no SNPs in exons1-4 of the AQP5 gene in our study population. However, the genotype frequency of +2254A>G SNP in intron3 was significantly different in cases and controls. The frequencies of AA AG GG in cases were 45.2%, 40.7%, and 14.1%, while in controls they were 34.5%, 51.6%, and 13.9% (chi2 = 9.899, P = 0.007), respectively. Higher OR for COPD was seen for persons with +2254AA genotype against +2254AG genotype (OR = 2.73; 95%CI = 1.88-3.97). Carriers of the variant allele +2254G had a lower risk of COPD than homozygous wild type carriers (OR = 0.44; 95%CI = 0.307-0.631).

CONCLUSION

The +2254A to G variant in intron 3 of AQP5 was associated with a decreased risk of COPD in a Chinese population.

摘要

背景

慢性阻塞性肺疾病（COPD）是慢性发病和死亡的主要原因。它受环境和遗传因素的影响。水通道蛋白5在维持正常肺水稳态中起关键作用。我们研究了水通道蛋白5基因多态性是否与个体患COPD的易感性有关。

方法

招募332例COPD患者和373名年龄匹配的无血缘关系的健康人作为研究对象。所有参与者均为中国汉族人。我们设计变性高效液相色谱法（DHPLC）检测水通道蛋白5（AQP5）外显子1、2、3中的单核苷酸多态性（SNP），并通过DNA测序进行确认。采用基于聚合酶链反应的限制性片段长度多态性方法对来自NCBI单核苷酸多态性数据库（dbSNP）的内含子3中的等位基因+2254A>G（rs3736309）和外显子4中的+3088A>G（苏氨酸-苏氨酸，rs41308104）进行基因分型。

结果

在我们的研究人群中，未在AQP5基因的外显子1-4中发现SNP。然而，内含子3中+2254A>G SNP的基因型频率在病例组和对照组中存在显著差异。病例组中AA、AG、GG的频率分别为45.2%、40.7%和14.1%，而对照组中分别为34.5%、51.6%和13.9%（χ2 = 9.899，P = 0.007）。+2254AA基因型个体患COPD的比值比（OR）高于+2254AG基因型个体（OR = 2.73；95%可信区间[CI] = 1.88-3.97）。变异等位基因+2254G的携带者患COPD的风险低于纯合野生型携带者（OR = 0.44；95%CI = 0.307-0.631）。