Department of Zoology, Government College University, Lahore, 54000, Pakistan.
Institute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
Mol Biol Rep. 2024 Oct 19;51(1):1070. doi: 10.1007/s11033-024-09983-8.
Type 1 diabetes (T1D) is an organ-specific autoimmune disorder characterized by the destruction of pancreatic β cells, leading to absolute insulin deficiency. The genes NLRP3, ICAM-1, PTPN22, and INS are reportedly associated with T1D in other populations. However, the genetic pattern of T1D in the Pakistani population is not clear. This study aimed to find the association of polymorphisms in the PTPN22, INS, NLRP3, and ICAM-1 genes with T1D susceptibility in the Pakistani population.
This case-control study includes 100 T1D patients (3-14 years), recruited randomly from the pediatric endocrinology department of Fatima Memorial Hospital, Lahore, Pakistan and 100 age-matched healthy controls were selected from different localities of the same population. The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing. The genotypic and allelic frequencies, haplotypes, and linkage disequilibrium were computed using the genetic toolset PLINK to investigate their relationship to T1D.
The results indicate that the occurrence of the GT genotype of the rs33996649 variant is significantly higher in children with T1D compared to a control group of healthy individuals (P = 0.001, OR: 2.0, 95% CI = 0.15-0.45). Furthermore, the CT genotype of rs2488457 was notably associated with T1D patients (P = 0.007, OR: 2.8, 95% CI = 0.56-0.67). The CG genotype of rs80356664 showed a slight association with T1D (P = 0.03, OR: 1.9, 95% CI = 0.35-0.59). The prevalence of the AT genotype of rs10754558 showed a strong association with T1D (P = 0.005, OR: 3.4, 95% CI = 0.45-0.69). The TG genotype of rs5498 was also strongly associated with T1D (P = 0.009, OR: 2.8, 95% CI = 0.75-0.89).
The present study provides evidence that SNPs in the PTPN22, INS, NLRP3, and ICAM-1 genes are associated with the development of T1D. Further research is needed to explore their potential use in genetic screening and personalized medication.
1 型糖尿病（T1D）是一种以胰腺β细胞破坏为特征的器官特异性自身免疫性疾病，导致绝对胰岛素缺乏。在其他人群中，NLRP3、ICAM-1、PTPN22 和 INS 基因据称与 T1D 相关。然而，巴基斯坦人群中 T1D 的遗传模式尚不清楚。本研究旨在探讨 PTPN22、INS、NLRP3 和 ICAM-1 基因多态性与巴基斯坦人群 T1D 易感性的关系。
本病例对照研究纳入了 100 名 T1D 患者（3-14 岁），随机从巴基斯坦拉合尔法蒂玛纪念医院儿科内分泌科招募；并从同一人群的不同地区选择了 100 名年龄匹配的健康对照者。采用 Sanger 测序法对 PTPN22（rs601、rs33996649、rs2488457）、INS（rs80356664）、NLRP3（rs10754558、rs35829419）和 ICAM-1（rs1799969、rs5498）基因的多态性进行基因分型。使用遗传工具集 PLINK 计算基因型和等位基因频率、单倍型和连锁不平衡，以研究它们与 T1D 的关系。
结果表明，与健康对照组相比，T1D 患儿 rs33996649 变体的 GT 基因型发生率明显更高（P=0.001，OR：2.0，95%CI：0.15-0.45）。此外，rs2488457 的 CT 基因型与 T1D 患者显著相关（P=0.007，OR：2.8，95%CI：0.56-0.67）。rs80356664 的 CG 基因型与 T1D 有轻微关联（P=0.03，OR：1.9，95%CI：0.35-0.59）。rs10754558 的 AT 基因型与 T1D 有很强的关联（P=0.005，OR：3.4，95%CI：0.45-0.69）。rs5498 的 TG 基因型与 T1D 也有很强的关联（P=0.009，OR：2.8，95%CI：0.75-0.89）。
本研究提供的证据表明，PTPN22、INS、NLRP3 和 ICAM-1 基因中的 SNPs 与 T1D 的发生有关。需要进一步的研究来探讨它们在遗传筛查和个体化药物治疗中的潜在应用。
