title: Human leukocyte antigen class I region single-nucleotide polymorphisms are associated with leprosy susceptibility in Vietnam and India.
abstract: Experimental evidence suggested the existence of unidentified leprosy susceptibility loci in the human leukocyte antigen (HLA) complex. To identify such genetic risk factors, a high-density association scan of a 1.9-mega-base (Mb) region in the HLA complex was performed. Among 682 single-nucleotide polymorphisms (SNPs), 59 were associated with leprosy (P <.01) in 198 Vietnamese single-case leprosy families. Genotyping of these SNPs in an independent sample of 292 Vietnamese single-case leprosy families replicated the association of 12 SNPs (P <.01). Multivariate analysis of these 12 SNPs showed that the association information could be captured by 2 intergenic HLA class I region SNPs (P = 9.4 × 10⁻⁹)-rs2394885 and rs2922997 (marginal multivariate P = 2.1 × 10⁻⁷ and P = .0016, respectively). SNP rs2394885 tagged the HLA-C*15:05 allele in the Vietnamese population. The identical associations were validated in a third sample of 364 patients with leprosy and 371 control subjects from North India. These results implicated class I alleles in leprosy pathogenesis.
authors: Research Institute of the McGill University Health Centre, McGill Centre for the Study of Host Resistance, Departments of Medicine and Human Genetics, McGill University, Montreal, Quebec, Canada.
authors: Andrea
authors: A
authors: Alter
authors: Nguyen Thu
authors: NT
authors: Huong
authors: Meenakshi
authors: M
authors: Singh
authors: Marianna
authors: M
authors: Orlova
authors: Nguyen
authors: N
authors: Van Thuc
authors: Kiran
authors: K
authors: Katoch
authors: Xiaojiang
authors: X
authors: Gao
authors: Vu Hong
authors: VH
authors: Thai
authors: Nguyen Ngoc
authors: NN
authors: Ba
authors: Mary
authors: M
authors: Carrington
authors: Laurent
authors: L
authors: Abel
authors: Narinder
authors: N
authors: Mehra
authors: Alexandre
authors: A
authors: Alcaïs
authors: Erwin
authors: E
authors: Schurr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D007918:Leprosy / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014744:Vietnam; D055815:Young Adult
chemical_list: D015395:Histocompatibility Antigens Class I