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BACKGROUND:Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established. OBJECTIVE:To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA. DESIGN:We performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 individuals of European descent. We also investigated relationships between specific single nucleotide polymorphisms (SNPs) in the lactase (LCT) gene, associated with adult-onset lactase intolerance, with circulating levels of dairy-derived OCSFA, and evaluated associations of candidate sphingolipid genes with C23:0 levels. RESULTS:We found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C15:0 or C23:0. In two cohorts with available data, we identified one intronic SNP (rs13361131) in myosin X gene (MYO10) associated with C17:0 level (P = 1.37×10-8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07×10-9). In contrast, when using a candidate-gene approach, we found evidence that three SNPs in LCT (rs11884924, rs16832067, and rs3816088) are associated with circulating C17:0 level (adjusted P = 4×10-2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P

Trans fatty acids (TFA) lower HDL and increase triglyceride concentrations while polyunsaturated fatty acids (PUFA) lower triglycerides and may decrease HDL concentrations. The effect of the interaction between trans fat and PUFA on lipids is uncertain.Men and women (n = 1032) in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) study were included. Fatty acids in erythrocyte membranes were measured with gas chromatography while data on potential confounders were obtained from questionnaires. To test the interaction between total erythrocyte PUFA (ePUFA) and TFA (eTFA) on lipid concentrations we distributed eTFA into tertiles and dichotomized ePUFA at the median concentration.For the 1(st), 2(nd) and 3(rd) tertiles of eTFA, multivariate-adjusted means±s.e.m for HDL were 46.2±1.1, 46.3±1.1 and 45.5±1.0 mg/dL among those with low ePUFA, respectively, while they were 50.0±1.1, 46.9±1.1 and 44.7±1.1 mg/dL among those with high ePUFA, respectively (P for interaction = 0.01). For the 1(st), 2(nd) and 3(rd) tertiles of eTFA, multivariate-adjusted means±s.e.m for triglycerides were 178.6±11.3, 144.7±10.9 and 140.8±10.6, respectively, among those with low ePUFA, while they were 133.8±11.3, 145.7±10.9 and 149.3±11.5, respectively, among those with high ePUFA (P for interaction = 0.005). Results for VLDL were similar to those for triglycerides. No significant interactions were observed for LDL or total cholesterol.The relation between trans fat and HDL, VLDL and triglycerides may depend on PUFA. The benefit of avoiding trans fat may be greater among individuals with higher PUFA intake. Supplementation with PUFA among individuals with relatively high trans fat intake may have limited benefits on lipid profiles.

The LDL receptor-related protein-1 gene (LRP-1) has been associated with obesity in animal models, but no such association has yet been reported in humans. As data suggest this increase in fat mass may be mediated through a mechanism involving the clearance of plasma triglyceride-rich lipoproteins (TGRL), where the LRP interacts with apolipoprotein E (ApoE) on chylomicron remnants, we aimed to examine (1) whether there was an association between 3 single nucleotide polymorphisms (SNPs) on LRP-1 with body mass index (BMI) and (2) whether any association between LRP-1 SNPs and BMI could be modified by polymorphisms on the ApoE gene when comparing the wild type ε3/ε3 genotype against mutant ApoE allele (ε2/ε4) carriers.We used data from 1,036 men and women (mean age ± SD = 49 ± 16 y) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. Mixed linear models, which controlled for age, sex, alcohol intake and smoking, as well as family pedigree and center of data collection were calculated. Models that used LRP-1 genotype as a predictor of BMI revealed that individuals who were homozygous for the minor allele at the LRP-1 I10701 locus had BMIs, on average, 1.03 kg/m(2) higher than major allele carriers (P = 0.03). In subsequent mixed linear models that included main effects of LRP-1 I10701 SNP and ApoE alleles, and an interaction term the two genotypes, there was no interaction detected between the LRP-1 I70701 genotype with either the ApoE ε2 or ε4 allele carriers (P>0.05).This has implications for starting to understand pathways from genotype to human BMI, which may operate through TGRL uptake at the LRP-1 receptor. This may pave the way for future research into individualized dietary interventions.

African Americans have been understudied in genome wide association studies of diabetes and related traits. In the current study, we examined the joint association of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the HyperGEN study, a family based study with proband ascertainment for hypertension. This analysis is restricted to 1,040 African Americans without diabetes. We generated allele specific CNV genotypes at 872,243 autosomal loci using Birdsuite, a freely available multi-stage program. Joint tests of association for SNPs and CNVs were performed using linear mixed models adjusting for covariates and familial relationships. Our results highlight SNPs associated with fasting insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10(-7)≤P≤1.1*10(-5)) near ATPase, class V, type 10A (ATP10A), and the L Type voltage dependent calcium channel (CACNA1D, rs1401492, P≤5.2*10(-6)). ATP10A belongs to a family of aminophospholipid-transporting ATPases and has been associated with type 2 diabetes in mice. CACNA1D has been linked to pancreatic beta cell generation in mice. The two most significant copy variable markers (rs10277702 and rs361367; P

Patients starting antiretroviral therapy (ART) for acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa have high rates of mortality in the initial weeks of treatment. We assessed the association of serum phosphate with early mortality among HIV-infected adults with severe malnutrition and/or advanced immunosuppression.An observational cohort of 142 HIV-infected adults initiating ART in Lusaka, Zambia with body mass index (BMI)