The HLA-DQB alleles and amino acid variants of the vitamin D-binding protein in diabetic patients in Alsace.
BACKGROUND
The HLA-DQB1 chain, in particular the amino acid in position 57, and genetic variants of the vitamin D-binding protein (DBP) have been reported to be associated with type 1 diabetes. There are two known polymorphisms in exon 11 of the DBP gene resulting in amino acid variants: codons 416 GAT --> GAG (Asp --> Glu) and 420 ACG --> AAG (Thr --> Lys). We compared distribution of DQB1 alleles and amino acid variants of DBP in type 1 diabetic patients (n = 44) in the Alsacian population and in healthy controls (n = 58).


METHODS
The second exon of the DQB1 gene and exon 11 of DBP were analyzed by restriction mapping after polymerase chain reaction.


RESULTS
A significant enrichment in DQB1 alleles encoding for an amino acid different from Asp in position 57 (NA) was observed in diabetic subjects as compared to controls (94.3 vs. 32.8%; p < 0.001). Combinations other than Ala/Ala carried the highest relative risk (OR = 52; p < 0.001). The analysis of the polymorphism in exon 11 of DBP showed a significant difference in the allele frequency of the HaeIII site, but not of the StyI site between patients and controls. Allele frequencies of HaeIII in diabetic subjects were 36% and 64% for Asp and Glu respectively (p < 0.001; chi(2) = 29.5). The frequency of Asp/Asp and Glu/Glu genotypes was increased in controls and diabetic subjects respectively. DBP alleles in individuals carrying the DQB1 NA combination revealed that 46.6% of diabetics were DBP Asp/Glu, but this was not statistically significant using the Fisher exact test (16/31 vs. 0/3; p = 0.23).


CONCLUSIONS
The study of the DQB1 chain confirmed the value of alleles encoding for an amino acid different from Asp in position 57 (NA) in the susceptibility to type 1 diabetes. The allele frequency of the HaeIII site, but not of the StyI site, differed between patients and controls (HaeIII p < 0.001; StyI p > 0.05).
Centre Européen d'Etude du Diabète-Hôpitaux Universitaires de Strasbourg, 67000, Strasbourg, France. jean-claude.ongagna@wanadoo.fr
J C
JC
Ongagna
M C
MC
Kaltenbacher
R
R
Sapin
M
M
Pinget
A
A
Belcourt
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002894:Chromosomes, Human, Pair 4; D003062:Codon; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005091:Exons; D005260:Female; D005602:France; D005787:Gene Frequency; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D014809:Vitamin D-Binding Protein / Q000235:genetics*
D003062:Codon; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D014809:Vitamin D-Binding Protein