Analysis of HLA-DQA1 and -DQB1 genes in Mexican Americans with insulin-dependent diabetes mellitus.
Mexican American patients (n = 35) with insulin-dependent diabetes mellitus (IDDM) and control subjects (n = 39) were HLA-DQA and DQB typed by the polymerase chain reaction technique combined with allele-specific oligonucleotide probes. Either DQB1*0302 or DQB1*0201 was present among 91% (32/35) of the patients compared to 67% (26/39) of controls. Either DQA1*0501 or DQA1*0301 was present in all patients (100% or 35/35) compared to 29/39 (74%) (OR 12.06 Pc < 0.05) of controls. All four of these genes, in cis or trans, were present in 15/35 (43%) of the patients compared to 3/39 (8%) of controls (OR 9.0; Pc < 0.01). The presence of one or more non-susceptibility alleles showed a dose-related decrease in relative risk. Presence of aspartic acid (Asp) at position 57 of the DQ beta chain did not confer protection and non-Asp homozygosity did not confer susceptibility to IDDM in this ethnic group. In conclusion, susceptibility to IDDM in Mexican Americans is associated with particular DQA and DQB combinations, illustrates dose-dependent parameters and contradicts the critical residue hypothesis.
Sanjeevi
C B
CB
Karolinska Institute, Dept. of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Zeidler
A
A
Shaw
S
S
Rotter
J
J
Nepom
G T
GT
Costin
G
G
Raffel
L
L
Eastman
S
S
Kockum
I
I
Wassmuth
R
R
D000328:Adult; D000483:Alleles; D015139:Blotting, Southern; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics*; D004198:Disease Susceptibility / Q000276:immunology; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D017058:Mexican Americans / Q000235:genetics*; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D015345:Oligonucleotide Probes