CD36 gene variants in early prediction of type 2 diabetes mellitus.

Type 2 diabetes (T2DM) is a noncommunicable disease affecting huge populations in India and abroad. Single-nucleotide polymorphisms (SNPs) in CD36, a macrophage scavenger receptor, have been implicated in the pathogenesis of T2DM and its complications. Eleven SNPs in the CD36 gene and their association with 100 each of control subjects and T2DM patients were investigated in the present study. The haplotype analysis of a few significant SNPs was carried out in individuals from families with diabetic history to evaluate its utility in disease prediction. Polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. Ten families with a family history of diabetes were identified and blood samples were collected from as many family members as possible. Genotyping of three SNPs, namely rs1761667 (G>A) in exon 1 A, rs3211938 (T>G) in exon 10, and rs3212018 (16 bp del) in exon 14, was performed in all samples. Our results suggested that individuals having a GATTC1 haplotype might be at risk of developing T2DM (p<0.001) and, therefore, might be susceptible to related complications. Moreover, the presence of A, G, and G alleles of SNPs rs1761667 (G>A), rs3211938 (T>G), and rs1984112 (T>G) tends to have increased BMI, respectively. Such studies may be helpful for disease prediction in individuals at risk of T2DM. The predictive potential of CD36 variants can be explored with more families in the study population to use this as a genetic marker.

CD36 gene variants and their association with type 2 diabetes in an Indian population.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a multifactorial disease resulting from ineffective use of insulin in the body. Single nucleotide polymorphisms (SNPs) in genes for scavenger receptors such as CD36 have been implicated in the pathogenesis of atherosclerosis and cardiovascular diseases in diabetes. The present study evaluated the effect of genetic polymorphisms of the CD36 gene on the risk of developing T2DM. Four SNPs in the CD36 gene (-178A→C in the promoter region, rs1984112 [A→G in exon 1A], rs1527479 [T→C in intron IB], and rs3211938 [T→G in exon 10]) were screened in T2DM patients and healthy controls (n=100 each). MATERIALS AND METHODS: Analysis of CD36 gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis was done by Fisher's exact test and χ² statistics using SPSS version 15.0 software (SPSS, Inc., Chicago, IL), whereas SHEsis software (available at http://analysis.bio-x.cn/myAnalysis.php ) was used for haplotype analysis. RESULTS: There was genotypic association of rs3211938 (T→G) polymorphism with T2DM (P=0.046), whereas rs1984112 (A→G) and rs1527479 (T→C) SNPs showed no association. The minor alleles of SNPs ("G" of rs1984112, "C" of rs1527479, and "G" of rs3211938) showed significant association with clinical profiles in T2DM patients (P<0.05). Analysis also showed that the "GCG" haplotype had a significant association with T2DM (P=0.026; odds ratio=3.12; 95% confidence interval 1.089-8.939). Significant association of the CD36 gene was confirmed by linkage disequilibrium patterns. CONCLUSIONS: The CD36 variants may help to determine the T2DM susceptibility in the North Indian population. However, genotyping of variants in more individuals and studies in other populations will be required to validate the results and ethnic variations.

Preliminary studies on CD36 gene in type 2 diabetic patients from north India.

BACKGROUND & OBJECTIVES: The greater tendency to diabetes in Indians may be due to genetic factors in addition to environment and diet. CD36, a class B scavenger cell surface receptor mediates internalization of oxidized low density lipoprotein (Ox-LDL) leading to the formation of macrophage foam cells. CD36 deficiency is related to phenotypic expression of the metabolic syndrome, frequently associated with atherosclerotic cardiovascular diseases resulting in raised levels of glucose thereby contributing to type 2 diabetes (T2DM). Therefore, the association of human CD36 gene mutation to T2DM needs investigation. We undertook this study to investigate CD36 gene status in north Indian subjects by screening for the deletion of exons 3, 4 and 5 and certain polymorphisms. METHODS: Clinical characteristics were compared between 300 T2DM patients and 100 healthy controls. Deletion analysis was carried out for exons 3, 4 and 5 of CD36 gene in 300 T2DM patients using PCR and agarose gel electrophoresis. Genotype analysis for two polymorphisms 478C>T and delAC in exons 4 and 5 respectively was carried out using PCR-RFLP method. RESULTS: Biochemical parameters such as fasting and post-prandial glucose levels, total cholesterol, LDL-cholesterol and blood pressure were slightly raised in the T2DM patients when compared with controls with lowered HDL-cholesterol. No exonic deletion was observed in the 300 patients and 100 controls screened. All individuals were found to be homozygous (CC and -/-) for the two polymorphisms studied. INTERPRETATION & CONCLUSIONS: Although no exonic deletion was found in T2DM patients, our study suggests that all 15 exons need to be screened for mutations which lead to CD36 deficiency. Genotyping studies of the two SNPs in the CD36 gene confirmed the absence of exons 4 and 5 deletion. This is perhaps the first report from India suggesting that CD36 is one of the several important genes that need to be explored in relation to T2DM.

The macrophage Ox-LDL receptor, CD36 and its association with type II diabetes mellitus.

Type II diabetes mellitus (T2DM) is a common and serious metabolic disorder worldwide. It is the third leading cause of death after cancer and cardiovascular disease (CVD). Over time, diabetes mellitus can lead to different complications like atherosclerosis, coronary heart disease and many micro- and macrovascular diseases. CD36 is a class B scavenger receptor whose expression is prevalent in vascular lesions. It has been shown that high plasma low density lipoprotein (LDL) levels become atherogenic when oxidized to modified LDL (Ox-LDL) by inducing foam cell formation via enhanced CD36 expression on macrophages. In addition to Ox-LDL, raised levels of glucose, insulin resistance, low HDL cholesterol, increased levels of free fatty acid (FFA) all result in increased expression of CD36, thereby contributing to T2DM and related atherosclerosis. Adipocytokines such as tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), adiponectin, leptin, resistin along with peroxisome proliferator activated receptor-γ (PPAR-γ) are important mediators in glucose homeostasis in association with CD36 and can be used as markers for T2DM and atherosclerosis. Several of these gene variants have shown association with lipid metabolism, T2DM and related complications. An attempt has been made to review the CD36 macrophage receptor and related molecules in association with T2DM.

Vitamin D receptor (FokI, BsmI and TaqI) gene polymorphisms and type 2 diabetes mellitus: a North Indian study.

BACKGROUND: The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to several diseases. Studies on association between VDR polymorphisms and risk of type 2 diabetes (T2DM) in different ethnic populations are yet inconclusive. AIMS: This study was conducted to evaluate association between VDR polymorphisms and genetic susceptibility to T2DM in the north Indian population. SETTINGS AND DESIGN: One hundred clinically diagnosed T2DM patients and 160 healthy controls from the north Indian population were recruited for genetic association study. MATERIALS AND METHODS: Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism SNPs of FokI (T/C) [rs2228570], BsmI (A/G) [rs1544410] and TaqI (C/T) [rs731236] by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. STATISTICAL ANALYSIS USED: Genotype distribution and allelic frequencies were compared between patients and controls. Mean values and odds ratios (ORs) with 95% confidence interval (CI) were calculated using SPSS software (version 15.0). RESULTS: The genotype distribution, allele and haplotype frequencies of VDR polymorphism did not differ significantly between patients and controls. Mean age and waist-hip ratio of patients were found to be associated with VDR polymorphism. Combination studies showed FFBbtt increased the risk of T2DM in north Indians. CONCLUSIONS: Our data suggest that VDR gene polymorphism in combination of genotypes is associated with the risk of T2DM and thus requires further studies as a probable genetic risk marker for T2DM.