汉族人群 FAM13A 多态性与 COPD 及 COPD 相关表型的相关性研究。

Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese.

机构信息

Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Clin Biochem. 2013 Nov;46(16-17):1683-8. doi: 10.1016/j.clinbiochem.2013.07.013. Epub 2013 Jul 25.

DOI:10.1016/j.clinbiochem.2013.07.013

PMID:23891779

Abstract

OBJECTIVES

Genome-wide association studies (GWAS) and integrative genomics approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and FAM13A polymorphisms in non-Asian populations. The aim of this study was to investigate whether FAM13A polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population.

METHODS

Seven single nucleotide polymorphisms (SNPs) (rs7671167, rs10007590, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) in FAM13A gene were genotyped in a case-control study (680 COPD patients and 687 controls). Allele frequencies and genotype distributions were compared between patients and controls. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested by using logistic regression analysis.

RESULTS

Statistical analysis revealed that SNP rs7671167 was associated with COPD in former smokers with adjusted P-value of 0.026. Five SNPs (rs7671167, rs2869966, rs2869967, rs2045517, and rs6830970) were associated with FEV1/FVC ratio in the entire cohort and rs6830970 was associated with FEV1/FVC ratio in COPD cases (P range 0.003-0.034). Borderline associations with FEV1/FVC ratio were found for rs2869966, rs2869967 and rs2045517 among cases (P=0.05). Six SNPs (rs7671167, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) showed strong linkage disequilibrium (r(2) ≥ 0.9). Four major haplotypes were observed but showed no significant difference between case and control groups (P=0.2356, 0.1273, 0.6266 and 0.3006 respectively).

CONCLUSIONS

The current study suggests that the FAM13A locus might be a contributor to COPD susceptibility in Chinese Han population.

摘要

目的

全基因组关联研究（GWAS）和综合基因组学方法已经证明，家族 13A（FAM13A）基因多态性与非亚洲人群的慢性阻塞性肺疾病（COPD）显著相关。本研究旨在探讨 FAM13A 基因多态性是否与中国汉族人群 COPD 的易感性和 COPD 相关表型有关。

方法

采用病例对照研究（680 例 COPD 患者和 687 例对照）对 FAM13A 基因中的 7 个单核苷酸多态性（SNP）（rs7671167、rs10007590、rs2869966、rs2869967、rs2045517、rs1903003、rs6830970）进行基因分型。比较病例组和对照组之间的等位基因频率和基因型分布。使用逻辑回归分析评估关联强度，计算优势比（OR）（95%CI），并检验潜在的混杂变量。

结果

统计学分析显示，SNP rs7671167 与调整后的前吸烟者 COPD 显著相关，调整后的 P 值为 0.026。在整个队列中，5 个 SNP（rs7671167、rs2869966、rs2869967、rs2045517 和 rs6830970）与 FEV1/FVC 比值相关，rs6830970 与 COPD 病例的 FEV1/FVC 比值相关（P 范围 0.003-0.034）。在病例中，rs2869966、rs2869967 和 rs2045517 与 FEV1/FVC 比值有边缘关联（P=0.05）。6 个 SNP（rs7671167、rs2869966、rs2869967、rs2045517、rs1903003、rs6830970）显示出很强的连锁不平衡（r²≥0.9）。观察到 4 个主要单倍型，但病例组和对照组之间无显著差异（P=0.2356、0.1273、0.6266 和 0.3006）。