Lifestyle Genomics最新文献

Background: "Quantile-dependent expressivity" is a dependence of genetic effects on whether the phenotype (e.g., insulin resistance) is high or low relative to its distribution.

Methods: Quantile-specific offspring-parent regression slopes (βOP) were estimated by quantile regression for fasting glucose concentrations in 6,453 offspring-parent pairs from the Framingham Heart Study.

Results: Quantile-specific heritability (h2), estimated by 2βOP/(1 + rspouse), increased 0.0045 ± 0.0007 (p = 8.8 × 10-14) for each 1% increment in the fasting glucose distribution, that is, h2 ± SE were 0.057 ± 0.021, 0.095 ± 0.024, 0.146 ± 0.019, 0.293 ± 0.038, and 0.456 ± 0.061 at the 10th, 25th, 50th, 75th, and 90th percentiles of the fasting glucose distribution, respectively. Significant increases in quantile-specific heritability were also suggested for fasting insulin (p = 1.2 × 10-6), homeostatic model assessment of insulin resistance (HOMA-IR, p = 5.3 × 10-5), insulin/glucose ratio (p = 3.9 × 10-5), proinsulin (p = 1.4 × 10-6), proinsulin/insulin ratio (p = 2.7 × 10-5), and glucose concentrations during a glucose tolerance test (p = 0.001), and their logarithmically transformed values.

Discussion/conclusion: These findings suggest alternative interpretations to precision medicine and gene-environment interactions, including alternative interpretation of reported synergisms between ACE, ADRB3, PPAR-γ2, and TNF-α polymorphisms and being born small for gestational age on adult insulin resistance (fetal origin theory), and gene-adiposity (APOE, ENPP1, GCKR, IGF2BP2, IL-6, IRS-1, KIAA0280, LEPR, MFHAS1, RETN, TCF7L2), gene-exercise (INS), gene-diet (ACSL1, ELOVL6, IRS-1, PLIN, S100A9), and gene-socioeconomic interactions.

The database at Nutrigenetics.net has been under development since 2007 to facilitate the identification and classification of PubMed articles relevant to human genetics. A controlled vocabulary (i.e., standardized terminology) is used to index these records, with links back to PubMed for every article title. This enables the display of indexes (alphabetical subtopic listings) for any given topic, or for any given combination of topics, including for genes and specific genetic variants. Stepwise use of such indexes (first for one topic, then for combinations of topics) can reveal relationships that are otherwise easily overlooked. These relationships include environmental and lifestyle variables with potential relevance to risk modification (both beneficial and detrimental), and to prevention, or at least to the potential delay of symptom onset for health conditions like Alzheimer disease among many others. Thirty-four specific genetic variants have each been mentioned in at least ≥1,000 PubMed titles/abstracts, and these numbers are steadily increasing. The benefits of indexing with standardized terminology are illustrated for genetic variants like MTHFR 677C-T and its various synonyms (e.g., rs1801133 or Ala222Val). Such use of a controlled vocabulary is also helpful for numerous health conditions, and for potential risk modifiers (i.e., potential risk/effect modifiers).

Background: Omentin is an adipokine with anti-inflammatory and insulin-sensitizing effects that can play a protective role against cardiovascular disease and diabetes. The aim was to systematically review and summarize the existing evidence on the association between overall dietary intake and omentin gene expression and circulation.

Summary: A literature search was conducted in PubMed, Scopus, and Web of Science up to September 2019. Of the 1,940 retrieved articles, 20 relevant studies were included, 6 of which were observational, 11 were clinical trials in humans, and 3 were animal studies. Four randomized controlled trials (RCTs) had a high risk of bias (RoB), 1 had "some concerns", and 2 had a low RoB. Among the nonrandomized studies with comparators, 4 had a serious RoB and 2 had a moderate RoB. In the experimental animal studies with a moderate RoB, conflicting results for omentin serum concentration were found for high-fat and low-fat diets. A high-fat diet (HFD) was shown to reduce omentin gene expression in one animal study. In the observational studies, omentin serum concentration was reduced by Ramadan fasting and saturated fatty acid (SFA) intake, and an increase in omentin gene expression was observed with monounsaturated fatty acid (MUFA) intake. There was no association of dietary inflammatory index (DII), macronutrient intake, or total calorie intake with omentin plasma concentrations. In the human interventional studies, omentin plasma concentration increased with a long-term low-calorie, low-fat diet (LFD), and no change was seen with a HFD or a short-term low-calorie diet (LCD). Key Messages: It seems that a long-term diet with a lower fat content and a balanced distribution of fatty acids, i.e., a higher MUFA and lower SFA intake, may effectively increase omentin plasma concentration, possibly via improved insulin resistance and reduced inflammation, but more research is needed to confirm or refute this.

Introduction: Single nucleotide polymorphisms (SNP) in the fat mass and obesity-associated (FTO) gene have been associated with type 2 diabetes (T2D) and its complications. The aim of the present research was to investigate which and how (directly or indirectly) clinical and metabolic variables mediate the association between fat mass and the FTO gene and early chronic kidney disease (CKD) in individuals with T2D.

Methods: This cross-sectional study was conducted in a sample of 236 participants with T2D (53.4% women, mean age 60 ± 10 years). DNA samples were genotyped for the rs7204609 polymorphism (C/T) in the FTO gene. Clinical, anthropometric, and metabolic data were collected. Path analysis was used to evaluate the associations.

Results: Of the sample, 78 individuals with T2D had CKD (33%). Presence of the risk allele (C) was higher among participants with CKD (21.8 vs. 10.8%; p = 0.023). This polymorphism was positively associated with higher waist circumference, which in turn was associated with higher glycated hemoglobin and higher blood pressure. A higher blood-pressure level was associated with higher urinary albumin excretion (UAE) and as expected, higher UAE was associated with CKD. Path analysis showed an indirect relationship between the FTO gene and early CKD, mediated by waist circumference, blood-pressure levels, and UAE.

Conclusions: These findings suggest that the C allele may contribute to genetic susceptibility to CKD in individuals with T2D through the presence of central obesity, hypertension, and high albuminuria.