Boletín Oficial de la Provincia de Oviedo: Número 131 - 1965 junio 9

Adults of Pacific descent residing in New Zealand have more than double the prevalence of diabetes, obesity, gout and the metabolic syndrome (MS), compared to the general population. Genetic, biochemical and environmental factors play a crucial role in the development of these diseases. These factors that predispose people of the Pacific, particularly Pacific adolescents, are poorly understood. Beginning 2013 the Pacific Trust Otago (PTO) in collaboration with the University of Otago recruited 80 Pacific Island young people (males = 33, females = 47) aged between 15 – 20 years residing in Dunedin. Participants, upon informed consent, were required to provide blood and urine samples to determine biochemical traits (e.g. serum urate, cholesterol, triglycerides etc.). Demographic and other lifestyle information were collated by means of questionnaires . DNA samples from this sample set were genotyped using Taqman genotyping. All (statistical) analyses were accomplished using STATA – a statistical software package. The most significant findings from this study are the association of alcohol with several outcomes, particularly body mass index (BMI). Alcohol consumption was significantly associated with increased BMI (Beta adjusted = 3.379, Padjusted = 0.03), and serum triglycerides (Betaadjusted = 0.236 mmol/L, Padjusted = 0.04) when adjusted by age and sex. At the crude level, alcohol consumption significantly caused an increase to diastolic blood pressures (Beta = 5.762 mm Hg, P = 0.004), and an increase in serum urate (Beta = 0.036 mmol/L, P = 0.02). Furthermore, this study provides evidence of association between BMI and serum urate adjusted for age and sex (Beta = 0.002 mmol/L, P = 0.05) and further, an association of BMI with increased triglycerides (Beta 0.027 mmol/L, P = 0.01). Physical activity correlated with reduced BMI, where moderately active participants had higher BMI (30.7 kg/m2) than those who were highly active (27.6 kg/m2). Genetics investigations provided no evidence of association of two variants of SLC2A9 (rs11942223 and rs3775948) with serum urate. Gene-environment interaction analysis also failed to provide any evidence of interaction between sugar and the genetic variants of the SLC2A9 for an influence on urate levels. The same account was made for the variants of the fat mass and obesity associated protein (FTO) (rs9922047 and rs9923233), tested for association with BMI. No evidence of association was established, with the gene-environment interaction test also unsuccessfully producing evidence of interaction between physical activity and the variants of the FTO gene, for an influence on BMI. Collectively, the findings from this research further support the notion that community based studies set out to evaluate risk factors for metabolic diseases ought to assess these factors in adolescents particularly those with high BMI values. The findings from this study are of importance for Pacific health by identifying pathways that could be targeted in treating and preventing metabolic disorders, to which Pacific people are more susceptible. These findings will also serve as a basis for allowing the PTO to set up intervention programs

A Polynesian-specific missense CETP variant alters the lipid profile

Summary: Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies