Mapping of a disease susceptibility locus in the HLA region for XXXX in Japan.

@entity2835 @entity1 @entity310 @entity69750 @entity1448
AIMS: @entity2835 ( @entity2835 ) is a chronic progressive @entity1448 of unknown pathogenesis. However, several reports have demonstrated the involvement of genetic backgrounds in this syndrome. The aim of this study is to examine the genetic disequilibrium in the HLA region in Japanese @entity1 using six microsatellite markers. METHODS: Genomic DNAs were obtained from 73 @entity1 with @entity2835 ( @entity1 cohort) and 186 healthy volunteers (control cohort). Genetic polymorphisms at six microsatellite markers (D6S1568, DQ.CAR, D6S273, @entity310 -d, @entity69750 ) were determined using fluorescence-labeled polymerase chain reaction (PCR) genetic analyzer. Allele frequencies were estimated by direct counting and the genotypic differentiation test was performed by the Markov chain method using Genepop software. RESULTS: Among these six microsatellite markers, four markers in the @entity1 significantly (P < 0.05) deviated from the Hardy-Weinberg equilibrium: DQ.CAR (P = 0.0278), D6S273 (P = 0.0168), @entity310 -d (P = 0.0089) and @entity69750 (P = 0.0005). Genotypic differentiation test between the @entity1 and controls demonstrated that DQ.CAR (P = 0.0111), @entity310 -d (P = 0.0051) and @entity69750 (P = 0.0371) were significant. Finally, allelic association test revealed before correction for multiple testing demonstrated allele125 of @entity310 -d (P = 0.00065, Pc = 0.0052) and allele246 of @entity69750 (P = 0.0026 Pc = 0.033) had significant association after Bonferroni's correction. CONCLUSION: Disequilibrium mapping using microsatellite markers was a useful method to narrow a disease susceptibility locus. The possible susceptibility gene in the HLA region is thought to be localized around or in the @entity310 gene. Further studies seem feasible using more closely distributed microsatellite markers or single nucleotide polymorphisms (SNPs) to narrow the susceptibility locus in @entity2835 in Japanese populations.
