Aslam Aqsa, Vijverberg Susanne J H, Zee Anke-Hilse Maitland-van der, Sabar Muhammad Farooq
Center for Applied Molecular Biology (CAMB), University of the Punjab, Lahore 54590, Pakistan.
Pulmonary Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Genes (Basel). 2024 Dec 17;15(12):1608. doi: 10.3390/genes15121608.
Genetic factors play a role in asthma severity. However, low- and middle-income countries have minimal contribution to genomic asthma research. The current study investigates the influence of an important genetic asthma region (6p21) on severe asthma in a cohort of asthmatics in Pakistan.
In this case-control study, mild to severe asthmatic patients ( = 255) and controls ( = 260) were enrolled from Lahore, Pakistan. Blood samples were collected, and genomic DNA was extracted for the genotyping of 11 single nucleotide polymorphisms located in the 6p21 region. Severe asthma was defined based on the defined daily dose of inhaled corticosteroids equivalent to 200 mcg of beclomethasone dipropionate (as per the global initiative for asthma guidelines). An additive genetic model was followed to find the associations between these variants and the outcome. Univariate and multivariate logistic regression, adjusted for confounders, was performed. Odds ratio (OR), 95% confidence interval (95% CI), -value, and q-values after FDR adjustment were estimated.
The genetic variants rs3025028, rs987870, and rs3025039 showed strong associations with the incidence of asthma with odds ratios of 1.58, 1.62, and 2.70 (95% CI = 1.16-2.16, 1.15-2.30, and 1.40-5.39, respectively). Further stratification analysis to study the risk of severe asthma also revealed markedly significant associations for rs3025020 and rs1799964 (OR = 2.28 and 2.99; 95% CI = 1.39-3.86 and 1.75-5.33, respectively). However, the SNPs rs2070600, rs987870, and rs3025039 also showed a significant relationship with the severity (OR = 2.34, 1.75, and 2.72; 95% CI = 1.02-5.97, 1.07-2.98, and 1.11-7.71, respectively), but FDR-adjusted q-values were insignificant (0.10, 0.07, and 0.07, respectively).
The 6p21 region variants rs3025028, rs987870, and rs3025039 are associated with the incidence, whereas rs3025020 and rs1799964 are associated with the risk of more severe asthma in the Pakistani population.
遗传因素在哮喘严重程度中起作用。然而，低收入和中等收入国家对基因组哮喘研究的贡献微乎其微。本研究调查了一个重要的遗传性哮喘区域（6p21）对巴基斯坦一组哮喘患者严重哮喘的影响。
在这项病例对照研究中，从巴基斯坦拉合尔招募了轻度至重度哮喘患者（n = 255）和对照者（n = 260）。采集血样，提取基因组DNA，对位于6p21区域的11个单核苷酸多态性进行基因分型。根据相当于200 mcg二丙酸倍氯米松的吸入性糖皮质激素的规定日剂量（根据全球哮喘防治创议指南）定义严重哮喘。采用加性遗传模型来寻找这些变异与结果之间的关联。进行了单变量和多变量逻辑回归，并对混杂因素进行了校正。估计了比值比（OR）、95%置信区间（95%CI）、P值以及经FDR校正后的q值。
基因变异rs3025028、rs987870和rs3025039与哮喘发病率密切相关，比值比分别为1.58、1.62和2.70（95%CI分别为1.16 - 2.16、1.15 - 2.30和1.40 - 5.39）。进一步的分层分析以研究严重哮喘的风险，结果还显示rs3025020和rs1799964有显著关联（OR = 2.28和2.99；95%CI分别为1.39 - 3.86和1.75 - 5.33）。然而，SNP rs2070600、rs987870和rs3025039也与严重程度有显著关系（OR = 2.34、1.75和2.72；95%CI分别为1.02 - 5.97、1.07 - 2.98和1.11 - 7.71），但经FDR校正后的q值不显著（分别为0.10、0.07和0.07）。
6p21区域变异rs3025028、rs987870和rs3025039与发病率相关，而rs3025020和rs1799964与巴基斯坦人群中更严重哮喘的风险相关。
