Vitamin D Receptor Gene Polymorphisms and HLA DRB1*04 Cosegregation in Saudi Type 2 Diabetes Patients

Abstract

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.

Vitamin D Status and its Receptor Genes BsmI, FokI, ApaI, TaqI Polymorphism in Relation to Glucose Metabolism in Obese Iraqi Type 2 Diabetes Mellitus Patients

“…Serum-ionized calcium and lipid profile decreased but not significantly in TC, TG, and LDL-C. All serum vitamin D levels were significantly lower in individuals with diabetic type 2 when compared to the controls as seen in Tables 2 and 3. There is no large scaled epid emiology study evaluating vitamin D deficiency in T2DM; however, several studies of different races have reported a high prevalence of hypo-vitaminosis D in patients with T2DM [27,28]. The distribution of vitamin D status in this study sample is very much in line with the study of 29 which found up to 98 percent of the subjects had vitamin D insufficiency or deficiency.…”

Vitamin D Receptor Gene Polymorphisms Are Associated with Obesity and Inflammosome Activity

“…It has been convincingly shown that the vitamin D/VDR axis modulates the activity of the immune system, and that in turn the immune system plays a pivotal role in vitamin D metabolism [20], [21]. Different reports suggest that chronic inflammation is a key marker of obesity, the origin of inflammation during obesity and the underlying molecular mechanisms that explain its occurrence are nevertheless not fully understood.…”

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease

“…The latter molecule increases the uptake of glucose in muscle and adipose tissue, whereas GLP-1 decreases glucagon production and increases the production of insulin in the pancreas. In addition, SCFAs possess the capacity to decrease gluconeogenesis in the liver by increasing the phosphorylation and activity of AMPK receptor (VDR) being a critical element in increased disease susceptibility [198]. It is, however, of interest that these authors reported VDR polymorphisms to be correlated with HLA-DRB1*04 and with metabolic and immunologic parameters [198] as reduced SCFAs would likely compound this association.…”