Association of CTLA-4 variation with type I diabetes in Filipinos.
The role of non-HLA single nucleotide polymorphisms from a panel of candidate genes in genetic susceptibility to type I diabetes (TID) among Filipinos was examined by PCR/SSOP typing of 90 patients and 94 controls, previously typed for the HLA class I and class II loci. We report the association of CTLA-4 A49G variation (cytotoxic T-lymphocyte associated-4) to TID among Filipinos, consistent with some but not all previous reports in other ethnic groups. The G allele frequency (0.61 versus 0.45, P=0.003) and GG genotype frequency (0.42 versus 0.22, P=0.004) were each increased in patients compared to controls, respectively. Among Filipinos, the CTLA-4 genotypes are associated with disease only in the presence of the predisposing DR3, 4, and 9 haplotypes (P=0.012). Compared to the AA genotype, the increased risk of diabetes predisposition is greatest in genotype GG bearing the DR susceptible alleles (DR3, 4, and 9) (odds ratio=4.6, P=0.001), demonstrating that non- HLA loci, acting in concert with HLA, can play potent roles in modifying susceptibility to TID.
Klitz
William
W
School of Public Health, University of California, 140 Warren Hall, Berkeley, CA 94720-7360, USA. klitz@socrates.berkeley.edu
Bugawan
Teodorica L
TL
Panelo
Araceli
A
Solfelix
Cecilia M
CM
Buzzetti
Raffaella
R
Pozzilli
Paolo
P
Steiner
Lori
L
Alejandrino
Maria
M
Erlich
Henry A
HA
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000276:immunology; D017209:Apoptosis; D044466:Asian People / Q000235:genetics*; D001327:Autoimmune Diseases / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D010679:Philippines / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D015234:HLA-A Antigens; D018796:Immunoconjugates; D000069594:Abatacept