Wake Forest University

About: Wake Forest University is a education organization based out in Winston-Salem, North Carolina, United States. It is known for research contribution in the topics: Population & Diabetes mellitus. The organization has 21499 authors who have published 48731 publications receiving 2246027 citations. The organization is also known as: Wake Forest College.

Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico

Abstract: Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings, we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P = 3.9 × 10(-13); odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P = 1.1 × 10(-4); OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at ~50% frequency in Native American samples and ~10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism.

Risk Factors for Preeclampsia, Abruptio Placentae, and Adverse Neonatal Outcomes among Women with Chronic Hypertension

Abstract: Background Women with chronic hypertension who become pregnant have an increased risk of preeclampsia and adverse neonatal outcomes. However, within this group, the risk factors for these adverse events are not known. Methods We analyzed data on outcomes for 763 women with chronic hypertension enrolled in a multicenter trial of low-dose aspirin for the prevention of preeclampsia. Preeclampsia was defined as new-onset proteinuria (urinary protein excretion, ≥300 mg per 24 hours) in the 682 women without proteinuria at base line. It was defined according to strict clinical criteria in the 81 women who had proteinuria at base line. The end points were maternal and neonatal outcomes. Results Among the 763 women, 193 (25 percent) had preeclampsia. The frequency of preeclampsia was not affected by the presence of proteinuria at base line (27 percent among women with proteinuria, vs. 25 percent among those without it), but it was greater in women who had had hypertension for at least four years (31 percent vs. 2...

Circulating Levels of Inflammatory Markers and Cancer Risk in the Health Aging and Body Composition Cohort

Abstract: Background: Chronic inflammation is associated with processes that contribute to the onset or progression of cancer. This study examined the relationships between circulating levels of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) and total as well as site-specific cancer incidence. Methods: Study subjects ( n = 2,438) were older adults (ages 70-79 years) participating in the Health Aging and Body Composition study, who did not report a previous cancer diagnosis (except for nonmelanoma skin cancer) at baseline. Incident cancer events ( n = 296) were ascertained during an average follow-up of 5.5 years. Inflammatory markers were measured in stored baseline fasting blood samples. Results: The adjusted hazard ratios (95% confidence intervals) for incident cancer associated with a 1-unit increase on the natural log-scale were 1.13 (0.94-1.37), 1.25 (1.09-1.43), and 1.28 (0.96-1.70) for IL-6, CRP, and TNF-α, respectively. Markers were more strongly associated with cancer death: hazard ratios were 1.63 (1.19-2.23) for IL-6, 1.64 (1.20-2.24) for CRP, and 1.82 (1.14-2.92) for TNF-α. Although precision was low for site-specific analyses, our results suggest that all three markers were associated with lung cancer, that IL-6 and CRP were associated with colorectal cancer, and that CRP was associated with breast cancer. Prostate cancer was not associated with any of these markers. Conclusions: These findings suggest that ( a ) the associations between IL-6, CRP, and TNF-α and the risk of cancer may be site specific and ( b ) increased levels of inflammatory markers are more strongly associated with the risk of cancer death than cancer incidence.