Association of serum 25-hydroxyvitamin D concentration with HLA-B, -DRB1 and -DQB1 genetic polymorphisms.
The human leukocyte antigen (HLA) gene region associates with the risk for several autoimmune diseases, including type 1 diabetes. An association between vitamin D deficiency and several autoimmune diseases has been suggested. We tested the association between serum 25-hydroxyvitamin D (25OHD) concentrations and HLA alleles in pregnant Finnish women.



HLA-B (n=395), HLA-DRB1 (n=501) and HLA-DQB1 (n=475) alleles were genotyped in pregnant women (mothers of children who later developed type 1 diabetes and mothers of non-diabetic children). HLA-B alleles were divided into supertypes that share similar peptide-binding specificity. Serum 25OHD concentration had been previously measured in these women from sera collected during the first trimester of pregnancy. Multiple testing was controlled for using the false discovery rate method.



An association was found between 25OHD concentration and HLA-B44 supertype (P=0.009); women with HLA-B44 supertype (B*18, B*37, B*40 and B*44 alleles) had lower 25OHD concentrations. No association was found between HLA-DRB1 or -DQB1 alleles and 25OHD concentration.



In this study we found for the first time an association between HLA genetic polymorphisms and 25OHD concentration. In future studies, the mechanistic background of this association and the role of vitamin D in the regulation of HLA gene expression should be investigated.
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
M E
ME
Miettinen
Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
L
L
Kinnunen
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.|Folkhälsan Institute of Genetics, Folkhälsan Research Center, University of Helsinki, Helsinki, Finland.|Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
V
V
Harjutsalo
Finnish Institute of Occupational Health, Helsinki, Finland.
K
K
Aimonen
Impact Assessment Unit, National Institute for Health and Welfare, Oulu, Finland.
H-M
HM
Surcel
Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
C
C
Lamberg-Allardt
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.|Center for Vascular Prevention, Danube-University Krems, Krems, Austria.|South Ostrobothnia Central Hospital, Seinäjoki, Finland.|Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.|Dasman Diabetes Institute, Dasman, Kuwait.
J
J
Tuomilehto
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D015235:HLA-B Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D014807:Vitamin D; C104450:25-hydroxyvitamin D