Rs2227982 and rs2227981 in PDCD1 gene are functional SNPs associated with T1D risk in East Asian
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 30 min post OGTT glucose level (P = 0.023) and 120 min 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.
KeywordsType 1 diabetes PDCD1 Polymorphism
We wish to thank Dr. Meng Zhu at Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, for his suggestions on the manuscript.
TY directed the study design, and critical revision of the manuscript. KX directed the study design, performed statistical analysis and interpretation of data, and drafted the initial manuscript. YG, WG, ZW, YC, YS and MZ contributed to collection and selection of samples. LX and SC were responsible for analysis and interpretation of data. JW reviewed and commented on various versions of the paper, and suggested revisions. All the co-authors gave final approval of the version.
The study was supported by Grants from the National Natural Science Foundation of China (81670715 and 81270897), Key Program of National Natural Science Foundation of China (81530026), the National Key Project of Research and Development Plan (2016YFC1305000), Jiangsu Province Youth Medical talents Project (QNRC2016584), the Jiangsu Province Key Science and Technology Development Project (BE2017753), Jiangsu Provincial Special Program of Medical Science (BL2012026), the Natural Science Foundation of Jiangsu province (BK2012486), Jiangsu Government Scholarship for Overseaas Studies (JS-2013-260), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Compliance with ethical standards
Conflict of interest
The authors declare that there is no duality of interest associated with this manuscript.
The study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University and carried out in agreement with the Helsinki II Declaration as revised in 2000.
Informed consent was obtained from all participants and/or their guardians in a written way.
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