Association of polymorphism of NLRP3, ICAM-1, PTPN22, INS genes in childhood onset type 1 diabetes in a Pakistani population.
PMID 39425874 | DOI 10.1007/s11033-024-09983-8 · Molecular biology reports · 2024 · View on PubMed ↗
BACKGROUND: 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. METHODOLOGY: 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. RESULTS: 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). CONCLUSION: 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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | NLRP3 | “Association of polymorphism of NLRP3, ICAM-1, PTPN22, INS genes in childhood onset type 1 diabetes in a Pakistani population.” | 0.98 | hgnc_dict_v1 |
| gene | PTPN22 | “Association of polymorphism of NLRP3, ICAM-1, PTPN22, INS genes in childhood onset type 1 diabetes in a Pakistani population.” | 0.98 | hgnc_dict_v1 |
| gene | INS | “Association of polymorphism of NLRP3, ICAM-1, PTPN22, INS genes in childhood onset type 1 diabetes in a Pakistani population.” | 0.98 | hgnc_dict_v1 |
| gene | TG | “The TG genotype of rs5498 was also strongly associated with T1D (P = 0.009, OR: 2.8, 95% CI = 0.75-0.89).” | 0.98 | hgnc_dict_v1 |
| phenotype | diabetes mellitus | “Association of polymorphism of NLRP3, ICAM-1, PTPN22, INS genes in childhood onset type 1 diabetes in a Pakistani population.” | 0.93 | phenotype_alias_lexicon_v2 |
| variant | rs601 | “The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing.” | 0.90 | hgvs_regex_v1 |
| variant | rs33996649 | “The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing.” | 0.90 | hgvs_regex_v1 |
| variant | rs2488457 | “The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing.” | 0.90 | hgvs_regex_v1 |
| variant | rs80356664 | “The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing.” | 0.90 | hgvs_regex_v1 |
| variant | rs10754558 | “The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing.” | 0.90 | hgvs_regex_v1 |
| variant | rs35829419 | “The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing.” | 0.90 | hgvs_regex_v1 |
| variant | rs1799969 | “The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing.” | 0.90 | hgvs_regex_v1 |
| variant | rs5498 | “The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing.” | 0.90 | hgvs_regex_v1 |