Association of HLA Class II and Non-HLA Gene Polymorphisms with Disease Susceptibility in Korean Children with Type 1 Diabetes Mellitus.

Jung,  Min Ho; Suh,  Byung Kyu; Kim,  Tai Gyu; Shin,  Choong Ho; Lee,  Byung Churl

Ann Pediatr Endocrinol Metab > Volume 9(2); 2004 > Article

Original Article

Journal of Korean Society of Pediatric Endocrinology 2004;9(2): 136-144.

Association of HLA Class II and Non-HLA Gene Polymorphisms with Disease Susceptibility in Korean Children with Type 1 Diabetes Mellitus.

Min Ho Jung, Byung Kyu Suh, Tai Gyu Kim, Choong Ho Shin, Byung Churl Lee

Abstract

Purpose : The main genetic contribution to type 1 diabetes susceptibility is the human leukocyte antigen (HLA) class II gene. Several non-HLA chromosomal regions are also known to be involved. We studied the association of HLA class II and non-HLA candidate genes, which are cytotoxic T lymphocyte antigen-4 (CTLA4), tumor necrosis factor (TNF), lymphotoxin-alpha(LT-alpha, and vitamin D receptor (VDR) gene, polymorphisms with disease susceptibility in Korean children with type 1 diabetes.Methods : Fifty Korean children with type 1 diabetes (29 girls and 21 boys) and 166 healthy Koreans were investigated in this study. HLA class II alleles were determined by PCR-SSP (sequence-specific primer) and PCR-SSOP (sequence specific oliogonucleotide probe) method. CTLA4 exon 1 polymor phism was analyzed by PCR-SSCP (single strand conformation polymorphism), and TNF promotor and LT-alphagene polymorphism by PCR-RFLP (restriction fragment length polymorphism), respectively. VDR gene polymorphisms were analyzed by PCR-RFLP using restriction enzyme FokI, ApaI, TaqI, and BsmI. Results : The frequencies of HLA-DRB1*04, DRB1*09, and DQB1*04 were significantly increased and those of HLA-DRB1*14, DRB1*15, DQB1*05 and DQB1*06 were significantly decreased in the patients with type 1 diabetes compared with the control subjects. No significant differences in the distribution of CTLA4 exon 1, TNF promotor, LT-alpha and VDR gene polymorphisms were observed between the patients with type 1 diabetes and the control subjects. Conclusion : These data suggest that HLA-DRB1*04, DRB1*09, and DQB1*04 are susceptible genes for type 1 diabetes, whereas HLA-DRB1*14, DRB1*15, DQB1*05, and DQB1*06 are protective genes in Korean children. CTLA4 exon 1, TNF promotor, LT-alpha and VDR gene polymorphisms are not associated with susceptibility to type 1 diabetes in Korean children.

Keywords: Type 1 diabetes;Gene;Susceptibility;Children