17q21变异与巴基斯坦普什图族人群哮喘易感性之间的关联。

Association between 17q21 variants and asthma predisposition in Pashtun population from Pakistan.

作者信息

Afzal Sibtain, Ramzan Khushnooda, Ullah Sajjad, Jamal Arshad, Basit Sulman, AlKattan Khaled M, Waqar Ahmed Bilal

机构信息

Department of Medical Laboratory Sciences, Faculty of Allied & Health Sciences, Imperial College of Business Studies, Lahore, Pakistan.

College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

出版信息

J Asthma. 2023 Jan;60(1):63-75. doi: 10.1080/02770903.2021.2025391. Epub 2022 Jan 26.

DOI:10.1080/02770903.2021.2025391

PMID:34982638

Abstract

OBJECTIVE

Asthma is a heterogeneous and genetically complex respiratory disease, and more than 300 million people are affected worldwide. In this study, frequencies of four SNPs (rs3816470, rs7216389, rs8067378, rs12603332) in chromosome 17q21 region were analyzed and their relationship with the asthma susceptibility, in the Pashtun population of Khyber Pakhtunkhwa province (KPK) of Pakistan were investigated.

METHODS

DNA samples from 500 subjects (asthma cases/controls) were genotyped by Sanger sequencing. Chi-square tests, logistic regression analysis, linkage disequilibrium, and haplotype analysis techniques were applied to study the association of the SNPs with asthma.

RESULTS

Genetic models, including recessive, dominant, co-dominant, over-dominant, and additive, were tested. The frequencies of alleles T/T at rs3816470 (OR = 1.91; 95%CI = 1.15-3.18; = ) and rs7216389 (OR = 2.14; 95%CI = 1.21-3.79; = ), A/A at rs 8067378 (OR = 1.89; 95%CI = 1.17-3.06; = ), C/C at rs12603332 (OR = 1.97; 95%CI = 1.18-3.27; = ), under recessive models, respectively, were significantly (-values < ) associated with asthma susceptibility. The frequencies of T/T genotype in rs3816470 (OR = 6.01; 95%CI = 2.48-14.60; = ), and rs7216389 (OR = 5.05; 95%CI = 1.79-14.21; = ), and C/C at rs12603332 (OR = 2.64; 95%CI = 1.11-6.32; = ), were significantly (-values < ) associated with asthma susceptibility in Pashtun women by stratified analysis based on age and gender. Similarly, three unique haplotypes were found associated with disease development and protective effect in female and male subjects. Linkage disequilibrium analysis presented a strong linkage (≥80%) between SNP variants and predicted their co-inheritance in the studied population.

CONCLUSION

The 17q21 variants (rs3816470, rs7216389, rs12603332) were found significantly (-values < ) associated with asthma predisposition in the Pashtun population of KPK exclusively in the female asthmatic cases.

UNLABELLED

Supplemental data for this article can be accessed.

摘要

目的

哮喘是一种异质性且遗传复杂的呼吸系统疾病，全球有超过3亿人受其影响。在本研究中，分析了17号染色体q21区域四个单核苷酸多态性（SNP，rs3816470、rs7216389、rs8067378、rs12603332）的频率，并研究了它们与巴基斯坦开伯尔-普赫图赫瓦省（KPK）普什图族人群哮喘易感性的关系。

方法

采用桑格测序法对500名受试者（哮喘病例/对照）的DNA样本进行基因分型。应用卡方检验、逻辑回归分析、连锁不平衡和单倍型分析技术研究SNP与哮喘的关联。

结果

对隐性、显性、共显性、超显性和加性等遗传模型进行了检验。在隐性模型下，rs3816470位点的T/T等位基因频率（OR = 1.91；95%CI = 1.15 - 3.18；P = ）、rs7216389位点的T/T等位基因频率（OR = 2.14；95%CI = 1.21 - 3.79；P = ）、rs8067378位点的A/A等位基因频率（OR = 1.89；95%CI = 1.17 - 3.06；P = ）、rs12603332位点的C/C等位基因频率（OR = 1.97；95%CI = 1.18 - 3.27；P = ）与哮喘易感性显著相关（P值 < ）。通过基于年龄和性别的分层分析，rs3816470位点的T/T基因型频率（OR = 6.01；95%CI = 2.48 - 14.60；P = ）、rs7216389位点的T/T基因型频率（OR = 5.05；95%CI = 1.79 - 14.21；P = ）以及rs12603332位点的C/C基因型频率（OR = 2.64；95%CI = 1.11 - 6.32；P = ）与普什图族女性哮喘易感性显著相关（P值 < ）。同样，发现三种独特的单倍型与女性和男性受试者的疾病发生及保护作用相关。连锁不平衡分析显示SNP变体之间存在强连锁（≥80%），并预测了它们在研究人群中的共同遗传情况。