Vitamin D receptor gene polymorphisms and HLA DRB1*04 cosegregation in Saudi type 2 diabetes patients.
The vitamin D receptor (VDR) gene has been involved in the modulation of susceptibility to inflammatory and autoimmune conditions, and could play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Susceptibility to T2DM was recently also suggested to associate with HLA alleles. We evaluated possible correlations between VDR polymorphisms, HLA alleles, and risk for development of T2DM by analyzing 627 individuals (368 T2DM patients and 259 healthy control subjects) part of a well-characterized cohort followed in Riyadh, Kingdom of Saudi Arabia. Genomic DNA was genotyped for the VDR gene single nucleotide polymorphisms of Fok-1, Taq-1, ApaI, and Bsm-I. Analyses were run by allelic discrimination real-time PCR. HLA genotyping was performed as well by PCR using sequence-specific primers, whereas cytokine production was evaluated by FACS. Results showed T2DM to be significantly associated with the VDR Taq1 (rs731236-AG) and Bsm-I (rs1544410-CT) genotypes, and the VDR rs1544410-T allele. Cosegregations resulting in significant increases of T2DM odds ratio were detected between Taq1 and Bsm-I VDR polymorphisms and HLA DRB1*04. Notably, the VDR polymorphisms observed to be more frequent in T2DM patients correlated with increased VDR expression and IL-12 production, as well as with metabolic parameters of susceptibility to T2DM, including serum cholesterol and high-density lipoprotein levels. VDR polymorphisms are present in T2DM, and correlate with HLA DRB1*04 and with immunologic and metabolic parameters; results from this study add T2DM to the list of diseases that are likely modulated by an HLA/VDR interaction.
Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia. aldaghri2011@gmail.com
Nasser M
NM
Al-Daghri
Omar
O
Al-Attas
Majed S
MS
Alokail
Khalid M
KM
Alkharfy
Hossam M
HM
Draz
Cristina
C
Agliardi
Abdul Khader
AK
Mohammed
Franca R
FR
Guerini
Mario
M
Clerici
D016022:Case-Control Studies; D020090:Chromosome Segregation; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D004198:Disease Susceptibility; D005828:Genetics, Population; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*; D012529:Saudi Arabia / Q000453:epidemiology
D059811:HLA-DRB1 Chains; D018167:Receptors, Calcitriol