Non-HLA genetic markers for Korean insulin-dependent diabetic patients

Background. Genes within the HLA class II region on chromosome 6 are the most important genetic factors for determining susceptibility to IDDM. However, they alone are not sufficient to account for the entire genetic contribution to this disease. Recent studies have demonstrated that LMP, TAP and other non-HLA genes such as the IDDM-2 (INS) and CTLA-4 genes are associated with susceptibility to IDDM in Caucasian subjects. Methods. 130 Korean IDDM patients were selected from the Korean Seoul Registry and 120 nondiabetic unrelated controls were recruited from the same geographic area. A total of 49 IDDM simplex families were also studied. The INS gene typing was studied by PCR-RFLP (Pst I+1127), and LMP7 polymorphisms were also identified by the same method using the restriction enzyme Hha I. Association analysis was used to evaluate a candidate region near the CTLA-4 gene using 49 Korean TDDM families as well as unrelated cases and controls. Results. The frequency of the INS +/+ homozygous genotype was not different between IDDM patients and controls (94.4 vs. 95.5%) and it was not polymorphic. There was no significant difference in the frequency of LMP7 A/A homozygotes between IDDM and controls (7.4 vs. 10.9%). Furthermore, when we divided and compared the subjects according to their HLA types (haploidentical subjects), we could not detect any association of the LMP7 A/A homozygous genotype with IDDM. The transmission/disequilibrium test (TDT) revealed a highly significant deviation of transmission for alleles at the A/G polymorphism within the CTLA-4 gene (p = 0.03). However, case/control comparisons could not confirm the association. Conclusions. We could assess that the polymorphism in the INS gene region or LMP7 region appeared to be of less value as a genetic marker for IDDM in Koreans. Non-HLA markers for IDDM such as the CTLA-4 gene might contribute to IDDM susceptibility in Koreans. Other candidate genes might be involved in IDDM susceptibility.