Faculty of Allied and Health Sciences, Imperial College of Business Studies, Lahore, Pakistan.
Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
Pak J Pharm Sci. 2020 Nov;33(6(Supplementary)):2729-2737.
Asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness and remodeling. Thymic stromal lymphopoietin (TSLP), a member of the interleukin-2 family of cytokines, is produced by activated lung and intestinal epithelial cells, mast, and other immune cells. Population-based studies identified associations between SNPs in the TSLP promoter region and asthma pathogenesis. In this study, we analyzed the genotypic association of TSLP rs1837253 with asthma predisposition in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Target DNA sequence of 250 asthmatics and an equal number of healthy individuals was PCR amplified, and allelic determination was performed by Sanger sequencing. Statistical analysis was conducted using chi-square tests and logistic regression analysis. Homozygous T/T genotype was frequent in the asthmatic subjects with a statistically significant level (P<0.05). Genetic models, including recessive, dominant, co-dominant, over-dominant, and additive were tested while adjusting allele frequencies with covariates (gender and age). Combined C/T and T/T individuals had higher odds ratios of 3.00, 1.91, and 1.73 in co-dominant, dominant, and additive models with statistically significant P-values of 0.029*, 0.022*, and 0.02*, respectively. T allele of rs1837253 was associated with increased susceptibility to asthma among Pashtuns, particularly in females, and we corroborate rs1837253 as a SNP of interest with a potential functional role.
哮喘是一种气道慢性炎症性疾病,其特征为气道高反应性和重塑。胸腺基质淋巴细胞生成素(TSLP)是白细胞介素-2 细胞因子家族的成员,由活化的肺和肠道上皮细胞、肥大细胞和其他免疫细胞产生。基于人群的研究确定了 TSLP 启动子区域 SNPs 与哮喘发病机制之间的关联。在这项研究中,我们分析了 TSLP rs1837253 与巴基斯坦开伯尔-普赫图赫瓦省普什图族人群哮喘易感性的基因型关联。对 250 例哮喘患者和相同数量的健康个体的目标 DNA 序列进行 PCR 扩增,并通过 Sanger 测序进行等位基因确定。使用卡方检验和逻辑回归分析进行统计分析。在哮喘患者中,纯合子 T/T 基因型较为常见,且具有统计学意义(P<0.05)。在调整协变量(性别和年龄)的等位基因频率后,测试了包括隐性、显性、共显性、超显性和加性在内的遗传模型。在共显性、显性和加性模型中,C/T 和 T/T 个体的合并具有更高的比值比(OR),分别为 3.00、1.91 和 1.73,且 P 值均具有统计学意义(分别为 0.029*、0.022和 0.02)。TSLP rs1837253 的 T 等位基因与普什图族人群哮喘易感性增加相关,特别是在女性中,我们证实 rs1837253 是一个具有潜在功能作用的感兴趣 SNP。