Genetic variation in vitamin D-related genes and risk of colorectal cancer in African Americans

PurposeDisparities in both colorectal cancer (CRC) incidence and survival impact African Americans (AAs) more than other US ethnic groups. Because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels, genetic variants that modulate the levels of active hormone in the tissues could explain some of the cancer health disparity. Consequently, we hypothesized that genetic variants in vitamin D-related genes are associated with CRC risk.MethodsTo test this hypothesis, we studied 39 potentially functional single-nucleotide polymorphisms (SNPs) in eight genes (CYP2R1, CYP3A4, CYP24A1, CYP27A1, CYP27B1, GC, DHCR7, and VDR) in 961 AA CRC cases and 838 healthy AA controls from Chicago and North Carolina. We tested whether SNPs are associated with CRC incidence using logistic regression models to calculate p values, odds ratios, and 95% confidence intervals. In the logistic regression, we used a log-additive genetic model and used age, gender, and percent West African ancestry, which we estimated with the program STRUCTURE, as covariates in the models.ResultsA nominally significant association was detected between CRC and the SNP rs12794714 in the vitamin D 25-hydroxylase gene CYP2R1 (p=0.019), a SNP that has previously been associated with serum vitamin D levels. Two SNPs, rs16847024 in the GC gene and rs6022990 in the CYP24A1 gene, were nominally associated with left-sided CRC (p=0.015 and p=0.018, respectively).ConclusionsOur results strongly suggest that genetic variation in vitamin D-related genes could affect CRC susceptibility in AAs. Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-014-0361-y) contains supplementary material, which is available to authorized users

Exenatide Treatment Alone Improves β-Cell Function in a Canine Model of Pre-Diabetes

BACKGROUND:Exenatide's effects on glucose metabolism have been studied extensively in diabetes but not in pre-diabetes. OBJECTIVE:We examined the chronic effects of exenatide alone on glucose metabolism in pre-diabetic canines. DESIGN AND METHODS:After 10 weeks of high-fat diet (HFD), adult dogs received one injection of streptozotocin (STZ, 18.5 mg/kg). After induction of pre-diabetes, while maintained on HFD, animals were randomized to receive either exenatide (n = 7) or placebo (n = 7) for 12 weeks. β-Cell function was calculated from the intravenous glucose tolerance test (IVGTT, expressed as the acute insulin response, AIRG), the oral glucose tolerance test (OGTT, insulinogenic index) and the graded-hyperglycemic clamp (clamp insulinogenic index). Whole-body insulin sensitivity was assessed by the IVGTT. At the end of the study, pancreatic islets were isolated to assess β-cell function in vitro. RESULTS:OGTT: STZ caused an increase in glycemia at 120 min by 22.0% (interquartile range, IQR, 31.5%) (P = 0.011). IVGTT: This protocol also showed a reduction in glucose tolerance by 48.8% (IQR, 36.9%) (P = 0.002). AIRG decreased by 54.0% (IQR, 40.7%) (P = 0.010), leading to mild fasting hyperglycemia (P = 0.039). Exenatide, compared with placebo, decreased body weight (P<0.001) without altering food intake, fasting glycemia, insulinemia, glycated hemoglobin A1c, or glucose tolerance. Exenatide, compared with placebo, increased both OGTT- (P = 0.040) and clamp-based insulinogenic indexes (P = 0.016), improved insulin secretion in vitro (P = 0.041), but had no noticeable effect on insulin sensitivity (P = 0.405). CONCLUSIONS:In pre-diabetic canines, 12-week exenatide treatment improved β-cell function but not glucose tolerance or insulin sensitivity. These findings demonstrate partial beneficial metabolic effects of exenatide alone on an animal model of pre-diabetes

Relative accuracy of body adiposity index and relative fat mass in participants with and without down syndrome

Background/Objectives: The body adiposity index (BAI) and relative fat mass (RFM) are anthropometric measures developed to estimate body composition (%Fat). There is limited research validating these methods of body composition assessment in adults with Down syndrome (DS). The aim of this study was to examine the accuracy of the BAI and RFM in a sample of adults with- and without DS. We hypothesize that the RFM would provide greater accuracy than the BAI when estimating %Fat. Subjects/Methods: BAI and RFM were assessed in a sample of adults (n = 235, 50.2% female, 20.0% DS, 23.1 ± 6.7 years). %Fat assessed using dual-energy X-ray absorptiometry served as the criterion method of body composition. Between-group differences were assessed using a two-way (SEX × DS) analysis of variance. Results: BAI overestimated %Fat in men without DS, but underestimated %Fat in women without DS (4.1 ± 4.5%Fat vs. −3.5 ± 4.6%Fat, respectively, p \u3c 0.001). BAI overestimated %Fat in men and women with DS (4.7 ± 7.8%Fat vs. 0.8 ± 7.5%Fat, respectively, p = 0.090). RFM slightly overestimated %Fat in male and female participants without DS, and did not vary by sex (0.9 ± 4.0%Fat vs. 0.2 ± 4.2%Fat, respectively, p = 0.248). RFM underestimated %Fat in men and women with DS, with no differences observed between sexes (−2.1 ± 5.3%Fat vs. −2.2 ± 6.9%Fat, respectively, p = 0.953). Conclusions: The BAI and RFM can be used to estimate body composition in individuals with- and without DS, however, the RFM yields greater accuracy and is recommended when more advanced methods of body composition assessment are unavailable or create unwanted participant burden