Vitamin D receptor gene polymorphisms are associated with adiposity phenotypes.

BACKGROUND: Emerging data suggest a role for the vitamin D receptor (VDR) in lipogenesis and adipocyte differentiation. OBJECTIVE: Our objective was to evaluate the association of VDR gene variants and adiposity phenotypes in an epidemiologic study. DESIGN: In a sample of 1773 healthy female adults recruited from western New York, we tested for the association of 14 VDR single nucleotide polymorphisms (SNPs) with the following 3 adiposity phenotypes: body mass index (in kg/m²), waist circumference (in cm), and abdominal height (in cm). We examined age, education, total energy intake, smoking status, alcohol intake, and menopausal status as potential covariates. RESULTS: One SNP, rs3782905, remained associated with all 3 adiposity phenotypes after multiple-testing correction (Bonferroni-adjusted P = 0.004). The mean waist circumference for women with the rs3782905 homozygous rare genotype was 4.4 cm larger than for women with the common homozygous genotype. Two other VDR SNPs were associated with waist circumference and abdominal height, but the associations did not survive multiple-testing correction. Adjustment for covariates did not influence the results. CONCLUSION: The study results and the biological activity of VDR in adipocyte differentiation suggest that 3' VDR variants may play a role in adiposity phenotypes.

Genetic polymorphisms of ATP-binding cassette (ABC) proteins, overall survival and drug toxicity in patients with Acute Myeloid Leukemia.

The overall survival of patients with acute myeloid leukemia (AML) remains poor due to both intrinsic and acquired chemotherapy resistance. Over expression of ATP binding cassette (ABC) proteins in AML cells has been suggested as a putative mechanism of drug resistance. Genetic variation among individuals affecting the expression or function of these proteins may contribute to inter-individual variation in treatment outcomes. DNA from pre-treatment bone marrow or blood samples from 261 patients age 20-85 years, who received cytarabine and anthracycline-based therapy at Roswell Park Cancer Institute between 1994 and 2006, was genotyped for eight non-synonymous single nucleotide polymorphisms in the ABCB1, ABCC1 and ABCG2 drug transporter genes. Heterozygous (AG) or homozygous (AA) variant genotypes for rs2231137 (G34A) in the ABCG2 (BRCP) gene, compared to the wild type (GG) genotype were associated with both significantly improved survival (HR=0.44, 95%CI=0.25-0.79), and increased odds for toxicity (OR=8.41, 95%CI= 1.10-64.28). Thus genetic polymorphisms in the ABCG2 (BRCP) gene may contribute to differential survival outcomes and toxicities in AML patients via a mechanism of decreased drug efflux in both, AML cells and normal progenitors.