Fatty acid desaturase (FADS) gene polymorphisms and insulin resistance in association with serum phospholipid polyunsaturated fatty acid composition in healthy Korean men: cross-sectional study

<p>Abstract</p> <p>Background</p> <p>We investigated the relationship between fatty acid desaturase (<it>FADS</it>) gene polymorphisms and insulin resistance (IR) in association with serum phospholipid polyunsaturated fatty acid (FA) composition in healthy Korean men.</p> <p>Methods</p> <p>Healthy men (n = 576, 30 ~ 79 years old) were genotyped for rs174537 near <it>FADS1 </it>(<it>FEN1</it>-10154G>T), <it>FADS2 </it>(rs174575C>G, rs2727270C>T), and <it>FADS3 </it>(rs1000778C>T) SNPs. Dietary intake, serum phospholipid FA composition and HOMA-IR were measured.</p> <p>Results</p> <p>Fasting insulin and HOMA-IR were significantly higher in the rs174575G allele carriers than the CC homozygotes, but lower in the rs2727270T allele carriers than the CC homozygotes. The proportion of linoleic acid (18:2ω-6, LA) was higher in the minor allele carriers of <it>FEN1</it>-10154G>T, rs174575C>G and rs2727270C>T than the major homozygotes, respectively. On the other hand, the proportions of dihomo-γ-linolenic acid (20:3ω-6, DGLA) and arachidonic acid (20:4ω-6, AA) in serum phospholipids were significantly lower in the minor allele carriers of <it>FEN1</it>-10154 G>T carriers and rs2727270C>T than the major homozygotes respectively. AA was also significantly lower in the rs1000778T allele carriers than the CC homozygotes. HOMA-IR positively correlated with LA and DGLA and negatively with AA/DGLA in total subjects. Interestingly, rs174575G allele carriers showed remarkably higher HOMA-IR than the CC homozygotes when subjects had higher proportions of DLGA (≥1.412% in total serum phospholipid FA composition) (<it>P </it>for interaction = 0.009) or of AA (≥4.573%) (<it>P </it>for interaction = 0.047).</p> <p>Conclusion</p> <p>HOMA-IR is associated with <it>FADS </it>gene cluster as well as with FA composition in serum phospholipids. Additionally, HOMA-IR may be modulated by the interaction between rs174575C>G and the proportion of DGLA or AA in serum phospholipids.</p

The peptidylglycine-α-amidating monooxygenase (PAM) gene rs13175330 A>G polymorphism is associated with hypertension in a Korean population

Abstract Background Peptidylglycine-α-amidating monooxygenase (PAM) may play a role in the secretion of atrial natriuretic peptide (ANP), which is a hormone involved in the maintenance of blood pressure (BP). The objective of the present study was to determine whether PAM is a novel candidate gene for hypertension (HTN). Results A total of 2153 Korean participants with normotension and HTN were included. Genotype data were obtained using the Korean Chip. The rs13175330 polymorphism of the PAM gene was selected from the ten single nucleotide polymorphisms (SNPs) most strongly associated with BP. The presence of the G allele of the PAM rs13175330 A>G SNP was associated with a higher risk of HTN after adjustments for age, sex, BMI, smoking, and drinking [OR 1.607 (95% CI 1.220–2.116), p = 0.001]. The rs13175330 G allele carriers in the HTN group treated without antihypertensive therapy (HTN w/o therapy) had significantly higher systolic and diastolic BP than the AA carriers, whereas the G allele carriers in the HTN group treated with antihypertensive therapy (HTN w/ therapy) showed significantly higher diastolic BP. Furthermore, rs13175330 G allele carriers in the HTN w/o therapy group had significantly increased levels of insulin, insulin resistance, and oxidized low-density lipoprotein (LDL) and significantly decreased LDL-cholesterol levels and LDL particle sizes compared to the AA carriers. Conclusion These results suggest that the PAM rs13175330 A>G SNP is a novel candidate gene for HTN in the Korean population. Additionally, the PAM rs13175330 G allele might be associated with insulin resistance and LDL atherogenicity in patients with HTN

A promoter variant of the APOA5 gene increases atherogenic LDL levels and arterial stiffness in hypertriglyceridemic patients.

Hypertriglyceridemia is recognized as an independent risk factor for coronary artery disease. The apolipoprotein A5 gene (APOA5) is a key regulator of triglyceride levels. We aimed to evaluate the associations of single nucleotide polymorphisms (SNPs) in APOA5, including -1131T>C and c.553G>T, with hypertriglyceridemia, apoA5 concentrations, atherogenic LDL cholesterol levels, and arterial stiffness in hypertriglyceridemic patients. The study population included 599 hypertriglyceridemic patients (case) and 1,549 untreated normotriglyceridemic subjects (control). We genotyped two APOA5 variants, -1131T>C (rs662799) and c.553G>T (rs2075291). The frequencies of the CC genotype of -1131T>C (0.165) and the T allele of c.553G>T (0.119) were significantly higher in hypertriglyceridemic patients than in normotriglyceridemic subjects (0.061 and 0.070, respectively; all pC and c.553G>T variants were associated with higher triglyceride and lower HDL cholesterol levels. Controls with the -1131CC variant had lower apoA5 concentrations than controls with the -1131TT variant. Similar effects of the -1131T>C variant on apoA5 were observed in the cases. In the hypertriglyceridemic group, the -1131T>C variant was associated with a smaller LDL particle size, higher levels of oxidized LDL and malondialdehyde, and higher brachial-ankle pulse wave velocity. The -1131T>C and c.553G>T polymorphisms were associated with hypertriglyceridemia in the study population, but only the -1131T>C polymorphism directly affected apoA5 concentrations. Hypertriglyceridemic patients carrying the APOA5 -1131T>C polymorphism exhibited increased atherogenic LDL levels and arterial stiffness, probably due to an effect of the -1131T>C polymorphism on apoA5 concentrations

Hyporesponsiveness of natural killer cells and impaired inflammatory responses in critically ill patients

Abstract Background To investigate natural killer (NK) cell activity, circulating cytokine level and peripheral blood mononuclear cell (PBMC) cytokine production status in critically ill patients. Methods Blood samples were collected <24 h after admission from 24 intensive care unit (ICU) patients and 24 age-, sex-, and body mass index (BMI)-matched healthy controls. Serum cytokine concentrations and cytokine production by PBMCs and lipopolysaccharide (LPS)-stimulated PBMCs were measured. Results The ICU group showed lower NK cell activity than the controls under all conditions and an absence of interferon (IFN)-γ. After adjusting for triglycerides, LDL- and HDL-cholesterol, and glucose, the ICU group exhibited lower serum levels of albumin and interleukin (IL)-12 and higher leukocyte counts and hs-CRP and IL-6 levels than the controls. Non-stimulated PBMCs from ICU patients secreted significantly greater amounts of IL-6 and IL-1β than the controls; however, the production of IL-6, TNF-α and IL-1β in response to LPS stimulation was significantly lower in the ICU group. Conclusions Significant reductions in NK cell activity and serum IL-12 level, an absence of serum IFN-γ, and decreased cytokine production from LPS-stimulated PBMCs indicate the hyporesponsiveness of NK cells and an impaired early phase inflammatory response in critically ill patients (ClinicalTrials.gov NCT02565589 :). Retrospectively registered; October 1, 2015

Associations of the <i>APOA5</i> -1131T>C polymorphism with apoA5 levels and serum lipid profiles in normotriglyceridemic controls and hypertriglyceridemic patients.

<p>Associations of the <i>APOA5</i> -1131T>C polymorphism with apoA5 levels and serum lipid profiles in normotriglyceridemic controls and hypertriglyceridemic patients.</p

Clinical and biochemical characteristics of controls and hypertriglyceridemic patients.

<p>Clinical and biochemical characteristics of controls and hypertriglyceridemic patients.</p

Associations of the <i>APOA5</i> c.553G>T polymorphism with apoa5 levels and serum lipid profiles in normotriglyceridemic controls and hypertriglyceridemic patients.

<p>Associations of the <i>APOA5</i> c.553G>T polymorphism with apoa5 levels and serum lipid profiles in normotriglyceridemic controls and hypertriglyceridemic patients.</p