The distribution characteristic of major histocompatibility complex class I chain- related gene A genotypes in autoimmune type 1 diabetes and its subgroups

Abstract

Objective To investigate the distribution characteristic of major histocompatibility complex (MHC) classⅠchain-related gene A (MICA) genotypes in different subgroups of autoimmune type 1 diabetes mellitus(T1DM) and its interaction with human leukocyte antigen (HLA)-DQ genotypes. Methods MICA and HLA-DQ genotypes were tested by PCR sequencing-base typing in patients with T1DM (n=338) and normal controls (n=258). The T1DM patients can be further diagnosed as T1ADM (n=193) and latent autoimmune diabetes in adults (LADA, n=145), who were outpatients in Institute of Metabolism Endocrinology and Department of Endocrinology or healthy subjects from physical examination, Second Xiangya Hospital, Central South University. Different alleles of MICA 4, 5, 5.1, 6, 9 were determined by the repeat sequence of GCT polymorphism in transmembrane domain at exon 5 of MICA gene. Chi square test was used to compare the frequencies of MICA gene in different subtypes of type 1 diabetes. Svejgaard Ryder test was used to analyze the interaction between MICA and HLA-DQ. Results (1)Some types of MICA alleles and genotypes were more frequent in early-onset T1ADM ( 20 years old) （χ2=0.067-3.078, χ2＝0.000- 3.954, all P>0.05）, LADA （χ2=0.000- 3.954, all P>0.05）and normal controls.(3)There was no linkage disequilibrium between MICA and HLA-DQ gene. Svejgaard Ryder test showed that the effect of MICA gene was weaker than HLA-DQ(OR(95%CI) ：0.266(0.114-0.625)), which can only have extra function when combined with susceptible HLA-DQ gene(3.037(1.448-6.370)). When HLA-DQ genes were protective or neutral, MICA gene show no susceptible effect （all P>0.05）. Conclusions MICA gene plays a role in T1ADM patients with susceptible HLA-DQ gene. The polymorphism of MICA gene is related to early-onset T1ADM, but not related to late-onset T1ADM and LADA. Key words: Diabetes mellitus, type 1; Major histocompatibility complex class Ⅰ chain-related gene A; Human leukocyte antigen-DQ; Genotype