Prevalence of ICA and anti-GAD, HLA DRB1 / DQA1 / DQB1 Polymorphism in Korean IDDM Patients

Park, Yong Soo; Shin, Jin Ho; Kim, Jin Bae; Choi, Woong Hwan; Ahn, You Hern; Kim, Tae Wha; Kim, Mok Hyun; Yang, Sei Won; Hwang, Seung Duck; Rhee, Hee Bal

Abstract

BACKGROUND: Although the HLA class II genes are cleaily associated with insulin-dependent diabetes mellitus(IDDM) in all ethnic. Groups, considerable variation in the associated genotypes is observed among the different ethnic groups. Mathods: In order to estimate what degree genetic and environmental determinants influence the true incidence of IDDM, ICA by imrnunohistochemistry, anti-GAD prevalence by radioimmunoprecipitation and HLA-DRB1, DQAl, and DQB1 polymorphisms after PCR amplification of genomic DNA were analyzed in 131 cases of IDDM, whose age at diagnosis were less than 15.
RESULTS
56% of them(73/131) were anti-GAD positive. 43% IDDM(56/131) were ICA positive. HLA DR3 and DR9 were susceptibility markers, whereas DR2 and DR5 were protective markers. DR3/4,, DR3/9, and DR3/X(X: other than 3, 4) were susceptible genotypes. HLA DQA1*0301 allele was increased, and DQB1*0301 and DQB1*0602 were decreased in IDDM. Not only HLA DQA1 Arg, but also DQBl non-Asp were found to be independent marker for IDDM, but their strength of association was weak. The highest prevalence of anti-GAD was observed in thosc homozygous for DR4(87.5%), exceeding that(47.8%) in those without this allele, and those with one DR4(63.5), whereas the highest prevealence of ICA was found in those homozygous for DR3(10G%), exceeding that in those with one DR3(64.3%) or in those without this allele(36.7%). There was a significant difference in numbers of HLA DQ susceptibility heterodimers in anti-GAD positive or negative patients. Conelusion: The prevalence of islet-specific auto-antibodies were present at comparable sensitivity and specificity in Korean IDDM patients. We could also assess that the immunoenetic markers for IDDM among Caucasians likewise confer disease susceptibility among Koreans. However, different HLA susceptibility alleles and a lower strength of association with known susceptibility markers, presumably because of differences in the genetic make-up of the population or in linkage disequilibrium patterns compared with other racial groups.