Gene frequencies and haplotypic associations within the HLA region in 916 unrelated Japanese individuals

Abstract

The gene frequencies and haplotypic associations within the HLA region have been investigated in 916 unrelated Japanese individuals. HLA class I and class II antigens were studied by conventional serology, and class II alleles, DRB1, DRB3, DQA1, DQB1 and DPB1 were typed by using polymerase-chain reaction amplification and sequence-specific oligonucleotide probe (PCR-SSOP) method. Thirty DRB1, 3 DRB3, 8 DQA1, 15 DQB1 and 13 DPB1 alleles were found in our population. DR-NJ25, a characteristic antigen in the native American and Asian populations, was observed at 3.0%. This antigen was observed mainly with the DRB1*1403 and 1406 alleles. Twenty-seven out of 30 DRB1 alleles found in this study had a high positive linkage disequilibrium with DQB1 alleles and 20 of them had an exclusive association with one specific DQA1-DQB1 combination. The strong association between DRB1 alleles and HLA-B antigens was the most striking finding in this study. Twenty-eight out of 30 DRB1 alleles had a positive linkage disequilibrium with 24 HLA-B antigens (p < 0.01). The other two alleles, DRB1*0404 and 1402, were very rare, and their frequencies were 0.2% and 0.1%, respectively. The data presented in this population study should be useful for the studies on anthropology, organ transplantation and disease susceptibility.

Neonatal lupus erythematosus: Haplotypic analysis of HLA class II alleles in child/mother pairs

“…These haplotype frequencies were significantly higher than those in the Japanese control population (5). The frequency of DRB1*0405-linked haplotypes was higher in the mothers than in controls.…”

“…Normal controls for HLA typing consisted of 916 unrelated race-matched subjects (5). DRBl/DQAl/DQBl haplotypes were assigned on the basis of known linkage disequilibria in Japanese subjects ( 5 ) along with data obtained in this study of childimother pairs. Fisher's exact test was used for statistical comparisons.…”

Good response to cyclosporine therapy in patients with myelodysplastic syndrromes having the HLA-DRB1*1501 allele

“…1,4 PTC is defined as a clinical pattern characterized by a syndrome of intracranial hypertension without signs of an intracranial spaceoccupying lesion or of an infectious process. 5 Our patient complained about abdominal discomfort during the first days of treatment and a mild elevation of alkaline phosphatase was noted. There was no further evidence of acute As 2 O 3 toxicity until the symptoms of elevated intracranial pressure occurred.…”

Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus

“…5 However, among the Japanese, strong linkage disequilibrium exists not only between HLA-DRB1 and HLA-DQB1 alleles, but also between HLA-DRB1 and HLA-B antigens, and these usually comprise characteristic haplotypes. 15,16 Therefore, extended HLA haplotype analysis is necessary for determining the HLA genes responsible for the pathogenesis of HCV-induced liver disease.…”

“…Haplotype analysis was based on population studies regarding the haplotype frequencies and linkage disequilibrium values for three-locus haplotypes (HLA-B-DRB1-DQB1) in the Japanese. 15,16 Statistical Analysis. The mean age, ALT value, and HCV RNA quantity of patients were compared by the Student' s t test or Mann-Whitney U test where appropriate.…”