Rs2227982 and rs2227981 in PDCD1 gene are functional SNPs associated with T1D risk in East Asian.

Abstract

To investigate whether PDCD1 gene polymorphisms are functional, and their associations with T1D risk and related clinical characteristics. A total of 3060 Chinese Han individuals (1019 T1D patients and 2041 healthy controls) were genotyped for 4 tag single nucleotide polymorphisms (SNPs) within the PDCD1 region (rs2227982, rs7421861, rs10204525, and rs6710479) and another most studied synonymous SNP, rs2227981. In addition, 251 healthy individuals underwent an oral glucose tolerance test (OGTT); measures of insulin release and sensitivity were estimated from insulinogenic, BIGTT, Matsuda. Further, we performed in silico bioinformatics analysis to explore potential functional annotation of the investigated SNPs in PDCD1 gene. Both rs2227982 and rs2227981 polymorphisms were associated with T1D risk in Chinese Han population under additive model (OR = 0.84, 95% CI 0.75-0.93 and OR = 1.23, 95% CI 1.08-1.40, respectively), but not the other three SNPs in PDCD1 gene. Our meta-analysis revealed that rs2227982 and rs2227981 polymorphisms also have significant associations with T1D risk in East Asians (OR = 0.82, 95% CI 0.74-0.90 and OR = 1.23, 95% CI 1.12-1.36, respectively), but not Europeans. And the T allele of rs2227982 polymorphism is associated with increased 30min post OGTT glucose level (P = 0.023) and 120min post OGTT insulin level (P = 0.033). Furthermore, the genetic and regulatory architecture suggested all the 5 investigated SNPs in PDCD1 are putatively functional. Both rs2227982 and rs2227981 polymorphisms were associated with T1D risk in East Asians, and rs2227982 also had a significant association with glycemic traits, which suggested PDCD1 gene polymorphisms might participate in facilitating T1D risk.