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

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.

Characteristics of patients with type 2 diabetes in México: Results from a large population-based nationwide survey

OBJECTIVE: To describe the clinical characteristics of the diabetic population that formed part of a population-based survey conducted in México.

RESEARCH DESIGN AND METHODS: In 2000, information was obtained from 42,886 subjects aged > or =20 years using a multistage sampling procedure. Standardized questionnaires were used. Anthropometric measurements, blood pressure, and capillary glucose concentrations were taken.

RESULTS: Type 2 diabetes was found in 3,597 subjects (age-adjusted prevalence 8.18%), of which 2,878 (80%) had previously been diagnosed. The average age of the diabetic participants was 55.2 +/- 13.5 years; 13% were <40 years of age. Nine percent had been diagnosed for >10 years. The average BMI was 29.2 +/- 5.7 kg/m(2); three-quarters of the cases had BMI >25 kg/m(2). The average waist circumference was 102 +/- 13.4 cm, and increased waist circumference was more common among women. Arterial hypertension was found in half of the cases and, of those on treatment, only one-third had a blood pressure <140/90 mmHg. Smoking was reported in 34% of the diabetic group, a higher rate than in the nondiabetic subjects. There was at least one modifiable coronary risk factor in 67.6% of the cases. Very few followed an exercise or dietary regimen and a small percentage used insulin.

CONCLUSIONS: Diabetes affects a large proportion of Mexican adults (8.18%). This figure may be underestimated. The majority of the subjects had modifiable risk factors for the chronic complications of diabetes. Only a few achieved adequate blood pressure control and other treatment goals.