D P Singal1, J Li, Y Zhu. 1. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. singald@fhs.csu.mcmaster.ca
Abstract
OBJECTIVE: We examined the contribution of the HLA class III region in susceptibility to rheumatoid arthritis (RA). METHODS: Patients with RA, healthy subjects and homozygous typing cell (HTC) lines were typed for HLA class I (A, B, C), class II (DR, DQ) and class III (D6S273, Bat 2, and TNFa microsatellites, and HSP70 promoter region) alleles by molecular techniques. RESULTS: Based on the distribution of microsatellites D6S273, Bat2 and TNFa, and HSP70 promoter region alleles in HTCs and homozygous unrelated individuals, a class III region haplotype, D6S273 138-HSP70c-Bat2 138-TNFa2 was identified. This haplotype showed a significant primary association with susceptibility to RA in DRB 1 QKRAA/QRRAA epitope-negative patients. CONCLUSION: Since the QKRAA/QRRAA epitope does not provide any risk for disease susceptibility in RA-susceptibility DRB1 epitope-negative patients, the present data suggest that the class III region haplotype D6S273 138-HSP70c-Bat2 138-TNFa2 provides an additional risk for the development of RA. These results show that two regions in MHC, class II (DRB1) and class III (D6S273 138-HSP70c-Bat 2 138-TNFa2), contribute to susceptibility to RA and more completely define the risk for development of the disease.
OBJECTIVE: We examined the contribution of the HLA class III region in susceptibility to rheumatoid arthritis (RA). METHODS:Patients with RA, healthy subjects and homozygous typing cell (HTC) lines were typed for HLA class I (A, B, C), class II (DR, DQ) and class III (D6S273, Bat 2, and TNFa microsatellites, and HSP70 promoter region) alleles by molecular techniques. RESULTS: Based on the distribution of microsatellites D6S273, Bat2 and TNFa, and HSP70 promoter region alleles in HTCs and homozygous unrelated individuals, a class III region haplotype, D6S273 138-HSP70c-Bat2 138-TNFa2 was identified. This haplotype showed a significant primary association with susceptibility to RA in DRB 1 QKRAA/QRRAA epitope-negative patients. CONCLUSION: Since the QKRAA/QRRAA epitope does not provide any risk for disease susceptibility in RA-susceptibility DRB1 epitope-negative patients, the present data suggest that the class III region haplotype D6S273 138-HSP70c-Bat2 138-TNFa2 provides an additional risk for the development of RA. These results show that two regions in MHC, class II (DRB1) and class III (D6S273 138-HSP70c-Bat 2 138-TNFa2), contribute to susceptibility to RA and more completely define the risk for development of the disease.
Authors: James R Cerhan; Stephen M Ansell; Zachary S Fredericksen; Neil E Kay; Mark Liebow; Timothy G Call; Ahmet Dogan; Julie M Cunningham; Alice H Wang; Wen Liu-Mares; William R Macon; Diane Jelinek; Thomas E Witzig; Thomas M Habermann; Susan L Slager Journal: Blood Date: 2007-09-07 Impact factor: 22.113
Authors: S J Wang; W J Liu; C A Sargent; S H Zhao; H B Liu; X D Liu; C Wang; G H Hua; L G Yang; N A Affara; S J Zhang Journal: Mol Biol Rep Date: 2011-06-12 Impact factor: 2.316
Authors: Mahamadou Diakite; Taane G Clark; Sarah Auburn; Susana Campino; Andrew E Fry; Angela Green; Andrew P Morris; Anna Richardson; Muminatou Jallow; Fatou Sisay-Joof; Margaret Pinder; Dominic P Kwiatkowski; Kirk A Rockett Journal: Hum Genet Date: 2008-11-28 Impact factor: 4.132