ERBB3-rs2292239 as primary type 1 diabetes association locus among non-HLA genes in Chinese

Chengjun Sun; Haiyan Wei; Xiuli Chen; Zhuhui Zhao; Hongwei Du; Wenhui Song; Yu Yang; Miaoying Zhang; Wei Lu; Zhou Pei; Li Xi; Jian Yan; Dijing Zhi; Ruoqian Cheng; Feihong Luo

doi:10.1016/j.mgene.2016.05.003

ERBB3-rs2292239 as primary type 1 diabetes association locus among non-HLA genes in Chinese

Meta Gene. 2016 May 12:9:120-3. doi: 10.1016/j.mgene.2016.05.003. eCollection 2016 Sep.

Authors

Chengjun Sun¹, Haiyan Wei², Xiuli Chen³, Zhuhui Zhao¹, Hongwei Du⁴, Wenhui Song⁵, Yu Yang⁶, Miaoying Zhang¹, Wei Lu¹, Zhou Pei¹, Li Xi¹, Jian Yan⁷, Dijing Zhi¹, Ruoqian Cheng¹, Feihong Luo¹

Affiliations

¹ Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai, China.
² Department of Pediatric Endocrinology, Children's Hospital of Zhengzhou, Zhengzhou, Henan, China.
³ Department of Pediatric Endocrinology, Soochow University Affiliated Children's Hospital, SuZhou, Jiangsu, China.
⁴ Department of Pediatric Endocrinology, First Affiliated Hospital of Jilin University, Changchun, Jilin, China.
⁵ Department of Pediatric Endocrinology, Children's Hospital of Shanxi Province, Taiyuan, Shanxi, China.
⁶ Department of Pediatric Endocrinology, Children's Hospital of Jiangxi Province, Nanchang, Jiangxi, China.
⁷ Science for Life Center, Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Stockholm, Sweden.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease that has strong contribution of genetic factors to its etiology. We aimed to assess the genetic association between non-HLA genes and T1D in a Chinese case-control cohort recruited from multiple centers consisting of 364 patients with T1D and 719 unrelated healthy children. We genotyped 55 single nucleotide polymorphisms (SNP) markers located in 16 non-HLA genes (VTCN1, PTPN22, CTLA4, SUMO4, CD274, IL2RA, INS, DHCR7, ERBB3, VDR, CYP27B1, CD69, CD276, PTPN2, UBASH3A, and IL2RB) using SNaPshot multiple single-base extension methods. After multivariate analysis and correction for multiple comparisons, we identified the SNP rs2292239 in ERBB3 gene were significantly associated with T1D. The frequency of the major G allele was significantly decreased in patients with T1D (68.8% in T1D vs 77.3% in controls, OR 0.65, 95% CI 0.53-0.79, P = 0.02), and the minor allele T was associated with an increased risk of T1D (OR 1.55, 95% CI 1.26-1.90, P = 0.02). Our haplotype analysis confirmed that rs2292239 was the primary T1D association locus in our current investigation. These results indicated that the ERBB3-rs2292239 was the primary T1D association locus among the investigated 55 SNPs in 16 non-HLA genes in Chinese Han population.

Keywords: CI, confidence interval; DNA, deoxyribonucleic acid; EGFR, epidermal growth factor receptor; ERBB3; GWAS, genome-wide association study; Genetic association; HLA, human leukocyte antigen; HWE, Hardy-Weinberg equilibrium; OR, odds ratio; SBE, single-base extension; SNP, single nucleotide polymorphism; Single nucleotide polymorphism; T1D, type 1 diabetes; Type 1 diabetes.