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PMID: 2881884 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Polymorphisms of DQ beta genes in HLA-DR4 haplotypes from healthy and diabetic individuals.

Immunogenetics ·Vol. 25 ·No. 3 ·1987-00-00 ·Pages 152-60

Henson V, Maclaren N, Riley W, Wakeland EK

Abstract

The restriction fragment length polymorphism (RFLP) of DQ beta was assessed in a panel of control and insulin-dependent diabetes (IDD) patients who were serologically typed as HLA-DR4 homozygotes or HLA-DR3, DR4 heterozygotes. Digestions of genomic DNA with Bam HI, Bgl II, Pst I, Xba I, and Hind III revealed a total of 15 RFLPs in the panel of 71 HLA-DR4 chromosomes. These RFLPs were organized into six allelic groups on the basis of segregation analysis in families. Complete RFLP haplotypes for the 5 restriction enzymes could be constructed for 42 of the HLA-DR4 chromosomes. This analysis revealed 18 RFLP haplotypes of DQ beta associated with the DR4 chromosomes tested. Two of these haplotypes, designated DQ3.DR4. a and DQ3.DR4.b, accounted for over 50% of the DR4 chromosomes analyzed. These two haplotypes were antithetical for the RFLPs detected by all five enzymes, indicating that they represent very distinct forms of DQ beta. The remaining 16 haplotypes were infrequent or unique and were closely related to either a DQ3.DR4.a or DQ3.DR4.b. Two of the RFLPs detected, a 5.8 kb Bgl II fragment and a 10.5 kb Bam HI fragment, had increased frequencies in disease-associated chromosomes. However, none of the RFLPs we detected exhibited a statistically significant increase in IDD or control populations. In contrast, the DQ3.DR4.b DQ beta haplotype was significantly decreased in IDD-associated DR4 chromosomes (P = 0.04). These results suggest that the DQ3.DR4.b DQ beta allele may be protective for the development of IDD.

MeSH Terms
Alleles Diabetes Mellitus, Type 1/genetics Gene Frequency Genotype HLA-D Antigens/genetics HLA-DR Antigens/genetics HLA-DR4 Antigen Haplotypes Humans Polymorphism, Genetic Polymorphism, Restriction Fragment Length
Chemicals
HLA-D Antigens HLA-DR Antigens HLA-DR4 Antigen
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Henson V
Maclaren N
Riley W
Wakeland E K
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34 references, click to expand
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Article Info
Journal
Immunogenetics
Abbr.
Immunogenetics
ISSN
0093-7711
DOI
10.1007/BF00344028
Published
1987-00-00
Pages
152-60
Language
English
Region
United States
NLM ID
0420404
Subset
IM
Grants
NIAID NIH HHS · AI-17966 · United States
NIADDK NIH HHS · AM 36151 · United States
NHLBI NIH HHS · HO 19469 · United States
External Links
PubMed source DOI: 10.1007/BF00344028 View journal details
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