Genetic variants in PNPLA3 but not APOC3 contribute to the variance in liver fat content due to NAFLD.

Our results indicate that IRS1 rs2943641 interacts with carbohydrate and fat intakes on incident T2D in a sex-specific fashion. A protective association between the rs2943641 T allele and T2D was restricted to women with low carbohydrate intake and to men with low fat intake.

The Ile148Met (rs738409, G-allele) in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) associates with liver fat content and may lead to loss-of-function (hydrolysis) or gain-of-function (CoA-dependent lysophosphatidic acid acyltransferase) defects. PNPLA3 is up-regulated by dietary carbohydrates, and interactions between rs738409 and carbohydrates, and sugar and ω6:ω3-polyunsaturated fatty acid (PUFA) ratio on hepatic fat accumulation have been reported. We examined interaction between rs738409 and overweight, and between rs738409 and dietary intakes (carbohydrates, sucrose and ω6:ω3-PUFA ratio), on fasting triglyceride levels. From the Malmo Diet and Cancer Study-Cardiovascular Cohort, 4,827 individuals without diabetes aged 58 ± 6 years, 2,346 with BMI ≤ 25 kg/m2 and 2,478 with BMI > 25 kg/m2, were included in cross-sectional analyses. Dietary data were collected by a modified diet history method. Overweight modified the association between rs738409 and fasting triglyceride levels (Pinteraction = 0.003). G-allele associated with lower triglycerides only among overweight individuals (P = 0.01). Nominally, significant interaction on triglyceride levels was observed between rs738409 and sucrose among normal-weight individuals (Pinteraction = 0.03). G-allele associated with lower triglycerides among overweight individuals in the lowest tertiles of carbohydrate and ω6:ω3-PUFA ratio (P = 0.04 and P = 0.001) and with higher triglycerides among normal-weight individuals in the highest tertile of sucrose (P = 0.001). We conclude that overweight and dietary sucrose may modify the association between rs738409 and fasting triglyceride levels.Electronic supplementary materialThe online version of this article (doi:10.1007/s12263-014-0388-4) contains supplementary material, which is available to authorized users.

M ore than 600 million people are estimated to be obese worldwide, 1 which is thought to be primarily a consequence of lifestyles characterized by consumption of energy-dense foods with poor nutritional content and lack of physical activity in the workplace and at home. The high prevalence of obesity is of considerable concern owing to the plethora of its life-threatening sequelae, including type 2 diabetes mellitus, coronary heart disease, and cerebrovascular disease.2 Accumulation of triglycerides in adipose, muscle, liver, and blood cells can impair cellular insulin action and glucose uptake and promote the accumulation of atherosclerotic arterial plaques.3,4 Therefore, elevated triglycerides and triglyceride-rich lipoproteins are important intermediate risk factors for type 2 diabetes mellitus and are causal Background-Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability. was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (P interaction =0.056). Meta-analyses of results from the Swedish cohorts yielded a statistically significant WGRS TG ×BMI interaction effect (P interaction =6.0×10 -4 ), which was strengthened by including data from the Danish cohorts (P interaction =6.5×10 -7 ). In the meta-analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRS TG ×BMI×sex) was observed (P interaction =0.03), where the WGRS TG ×BMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci. Conclusions-Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females. (Circ Cardiovasc Genet. 2016;9:162-171.

Kritièno oboleli su bolesnici sa životno ugrožavajuaeim multiorganskim poremeaeajima. U veaeini sluèajeva nastanku životno ugrožavajuaeeg stanja prethodi pogoršanje osnovnih vitalnih parametara, što se èesto previdi u vanhospitalnim i hospitalnim uslovima. Iz tih razloga je sistematsko praaeenje vitalnih parametara od velikog znaèaja a u tom cilju i uvodjenje u svakodnevni rad, pre svega u bolnièkim uslovima, bodovnih sistema za rano prepoznavanje životno ugroženih bolesnika. Postoji više ovih bodovnih sistema, od kojih se najèešaee koriste ranoupozoravajuaei bodovni sistemi koji prate vitalne parametre kao što su srèana frekvencija, krvni pritisak, disajna frekvencija, tem per a ture, saturacija periferne krvi kiseonikom i/ili diureza, promene mentalnog statusa. Brojnim istraživanjima je dokazana važnost primene ovih sistema u svakodnevnom klinièkom radu radi pravovremenog prepoznavanja životno ugroženih bolesnika u hos pi talnim uslovima u cilju smanjivanja mortaliteta. Prema rezultatima nekih studija ovi bodovni sistemi imaju i prognostièki znaèaj. Kljuène reèi: životno ugroženi bolesnici, ranoupozoravajuaei bodovni sistemi UVOD U vanhospitalnim i hospitalnim uslovima životno ugroženi bolesnici se èesto ne prepoznaju na vreme što je direktno povezano sa visokom stopom mortaliteta kod ovih bolesnika. Definicija životno ugroženih bolesnika Životno ugroženi bolesnici su bolesnici èije opšte stanje (disfunkcija ili bolest više organa i/ili organskih sistema), prognoza i preživljavanje zavise od primene savremene tehnike i terapije. To su bolesnici koji imaju