Association of variants inPTPN22,CTLA-4,IL2-RA, andINSgenes with type 1 diabetes in Emiratis

Type 1 diabetes (T1D) is a chronic autoimmune disease with a complex interrelation of genetic and environmental factors. Genetic studies have reported HLA and non-HLA loci as significant contributors to T1D. However, the genetic basis of T1D among Emiratis is unexplored. This study aims to determine the contribution of four genesPTPN22,CTLA-4,IL2-RA, andINSto T1D risk among Emiratis. The association between variants inPTPN22(rs2476601, rs1310182),CTLA-4(rs11571316, rs231775, rs3087243, rs1427676, and rs231727),IL2-RA(rs7090530), andINS(rs7111341) with T1D was tested in 310 Emiratis (139 T1D patients and 171 controls). A significant association was found at rs1310182, and rs2476601 both inPTPN22, rs3087243, and rs231775 both inCTLA-4, and rs12251307 inIL2-RA. Moreover, a haplotype constituted from GG and AG genotypes at rs231727 and rs231775, respectively, inCTLA-4was significantly associated with an increased T1D risk. The cumulative effects of risk alleles for all significantly associated SNPs showed 11.8 higher relative risk for T1D for those who carry 5-6 compared to 0-1 risk alleles. This study illustrated thatPTPN22, CTLA-4, andIL2-RAgene variants could confer risk alleles for T1D among the Emirati population.

Automated summary

This study found significant associations between variants in PTPN22, CTLA-4, and IL2-RA genes and Type 1 diabetes risk among Emiratis, indicating that these gene variants could be risk alleles for T1D in the Emirati population. Moreover, a haplotype in CTLA-4 was significantly associated with increased T1D risk, and the cumulative effects of risk alleles showed a higher relative risk for T1D in individuals carrying more risk alleles.