The DQw7 allele at the HLA-DQB locus is associated with susceptibility to IgA nephropathy in Caucasians.
The frequencies of the MHC class II HLA-DR and DQ alleles in 36 Caucasian patients with IgA nephropathy (IgAN) were analyzed by RFLP analysis and allele specific oligonucleotide (ASO) probing of specifically amplified genomic DNA. The class II alleles HLA-DR4 (52.7%) and DR5 (30.5%) were increased in the patient group compared to 1103 UK Caucasoid controls, but these increases were not statistically significant. However, there was a significant increase in the HLA-DQw7 allele frequency (71%) (c = 27.8%, chi 2 = 29.2, P less than 0.001, Relative Risk = 6.17). This can be explained by linkage disequilibrium between the DQw7 allele at the DQB1 locus and DRB1 genes of some DR4 and all DR5 haplotypes. The polymorphic portion of the DQ alpha chains from DR4, DQw7 and DR5, DQw7 haplotypes differ but they have identical DQ beta chains. DNA encoding DQw7 allele at the DQB1 locus was sequenced in two patients and was identical to that previously published. We conclude that the DQw7 allele at the DQB1 locus is strongly associated with susceptibility to IgAN in Caucasians.
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
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D000483:Alleles; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000032:analysis; D005787:Gene Frequency; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D044465:White People
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069546:HLA-DQ7 antigen; C057615:HLA-DQbeta antigen; D006684:HLA-DR Antigens; D015345:Oligonucleotide Probes; D004247:DNA