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.

Characterization & evolutionary analysis of human CD36 gene.

Background and objectives: Understanding evolutionary genetic details of immune system genes responsible for infectious diseases is of prime importance concerning disease pathogenecity. Considering malaria as a devastating disease in the world including India, detail evolutionary understanding on human immune system gene is essential. The primary aim of this study was to initiate work on one such gene, the human CD36 gene responsible in malaria pathogenesis. Methods: DNA sequences of the human CD36 gene was retrieved from public domain and fifi ne-scale details were characterized. Both comparative and evolutionary analyses were performed with sequences from six other taxa (5 mammalian one avian) where CD36 homologs are present. Different statistical analyses were also performed. Results: Differential distribution in number and length of exons and introns was detected in CD36 gene across seven taxa. The CpG islands were also found to be distributed unevenly across the gene and taxa. Neighbour-joining tree was constructed and it was observed that the chimpanzee and human are diverged at the CD36 gene relatively recently. The chicken, Gallus gallus was found to be diverged from rest of the taxa signifi cantly. Also copy number variation was observed across different taxa. Interpretation & conclusions: Comparative genomic study of a human immune system gene CD36 show relationships among different taxa at the evolutionary level. The information can be of help to study genetic diversity in malaria endemic zones and to correlate it with malaria pathogenecity.

Relation of the CD36 gene A52C polymorphism to the risk of colorectal cancer among Japanese, with reference to with the aldehyde dehydrogenase 2 gene Glu487Lys polymorphism and drinking habit.

High consumption of white meat (or saturated fatty acids) and alcohol has been demonstrated to have a tendency to increase the risk of colorectal cancer, according to the level of malondialdehyde-deoxyguanosine adducts derived from lipid per-oxidation in the colorectal mucosa. CD36 plays important roles as a long-chain fatty acid translocase and oxidized low-density lipoprotein (LDL) scavenger, while alcohol is metabolized by aldehyde dehydrogenase 2 (ALDH2) and decreases transiently metabolism of dietary fat and serum lipids. To examine associations between the risk of colorectal cancer and the CD36 gene A52C polymorphism according to the ALDH2 gene Glu487Lys polymorphism and drinking habit, a hospital-based case-control study was conducted with 128 colorectal cancer cases and 238 cancer-free controls. Odds ratios (ORs) for the C/C genotype relative to the A/A genotype were 1.70 [95% confidence interval (CI), 0.76-4.11] and 4.24 (95% CI, 1.42-22.66) for men and women, respectively, with the low-activity (Glu/Lys + Lys/Lys) ALDH2 genotype. The high-activity (Glu/Glu) genotype for men and women had no associations. On the other hand, the OR for the C/C genotype with high frequency of drinking habit relative to the A/A genotype with low frequency of drinking habit among men was 3.63 (95% CI, 1.29-13.15). The number of women with a high frequency drinking habit was too small for any corresponding analyses. Our findings suggest a significant interaction between alcohol consumption and the CD36 gene A52C polymorphism related to the metabolism of long-chain fatty acids and oxidized LDL in the etiology of colorectal cancer.

Polymorphisms of CD36 in Thai malaria patients.

The human protein CD36 is a major endothelial receptor for Plasmodium falciparum parasitized erythrocytes. Several polymorphisms causing CD36 deficiency have been identified to date: T1264G in Kenyan and Gambian patients, and C478T, 539delAC, and 1159insA in Japanese patients. The T1264G polymorphism is reportedly associated with protection from severe malaria in Kenyans, although there is a contradictory report suggesting the susceptibility of T1264G to severe malaria. The polymorphism of CD36 has not been thoroughly studied in Asian malaria patients. In this study, nucleotide sequence variations in exons 4, 5, 6, and 10 of CD36 were investigated in mild and cerebral malaria patients living in northwest Thailand. A novel synonymous substitution T1168C was detected in exon 10, whereas no variation was found in exons 4 and 6. The 539delAC allele in exon 5 was detected in Thai malaria patients, while T1264G, C478T, and 1159insA were not found. The 539delAC allele was observed in three cerebral malaria patients (3/107), but not in mild malaria patients (0/203). The frequency of 539delAC was significantly higher in cerebral malaria patients than in mild malaria patients (p = 0.040, Fisher's exact test). Although independent studies should be performed in order to confirm our findings, the 539delAC allele might be a high-risk variant for cerebral malaria in Thai.