Lifestyle Genomics最新文献

Introduction: Obesity is a prevalent multifactorial disease whose main complication is dyslipidemia. Serum lipid levels also depend on genetic factors including the Taq1B variant of the CETP gene, which is suggested to be influenced by environmental factors and adiposity. Therefore, this study aimed to determine the effect of the Taq1B CETP variant on serum lipid levels associated with anthropometrical variables.

Methods: 165 women from western Mexico were enrolled in this cross-sectional study. Weight and body fat were measured by bioimpedance and waist circumference with a measuring tape. Serum lipid levels were determined by dry chemistry. The Taq1B CETP variant was analyzed by allelic discrimination.

Results: Women with abdominal obesity and the B1B2/B2B2 genotype had significantly higher total cholesterol levels (195.17 [185.95-204.39] vs. 183 mg/dL [169.83-196.16], p = 0.007) and low density lipoprotein (118.84 [110.65-127.03] vs. 113.84 mg/dL [102.37-125.31], p = 0.037) than carriers of the B1B1 genotype. Likewise, subjects with excessive adiposity and the B1B2/B2B2 genotype showed significantly higher total cholesterol levels (195.05 [186.04-204.06] vs. 182.40 mg/dL [169.03-195.76], p = 0.003) than those with the B1B1 genotype.

Conclusion: Women with abdominal obesity or excessive adiposity, who are also carriers of the B1B2/B2B2 genotype, have higher serum lipid levels than women with the B1B1 genotype.

Introduction: The fat mass and obesity-associated gene (FTO) is largely/primarily expressed in the hypothalamus. It plays a role in energy balance, regulation of food intake, and adipogenesis. According to metabolic phenotypes, studies have associated the FTO rs9939609 variant with body mass index (BMI), body fat mass, and dietary intake but not with serum lipids. This study aimed to analyze the association of the FTO rs9939609 variant with serum lipids in Mexican adults with different metabolic phenotypes.

Methods: We included 306 subjects aged 18-65 years, classified as normal weight or excess weight (EW) according to their BMI. EW included BMI from 25 to 39.9 kg/m2. Participants were classified into two metabolic phenotypes: metabolically healthy/metabolically unhealthy (MH/MUH). We use the homeostatic model assessment of insulin resistance and NCEP-ATP III cutoffs for glucose, triglycerides, high-density lipoprotein, and blood pressure. Subjects with ≥2 altered parameters were classified as MUH. The variant was determined by allelic discrimination with TaqMan® probes.

Results: In subjects with the A allele, significantly higher total cholesterol and low-density-lipoprotein cholesterol were found (p < 0.05). Furthermore, subjects with EW-MH and the AA or AT genotype had a significantly higher odds ratio for hypercholesterolemia (odds ratio 4.48, 95% confidence interval: 1.48-13.59, p = 0.008).

Conclusion: The FTO rs9939609 variant may influence serum lipid concentrations, increasing the risk of hypercholesterolemia.

Introduction: In mammals, circadian rhythms regulate many behavioral and physiological processes. Genetic and epidemiological studies have shown that dysregulation of the circadian rhythm induces chronic metabolic diseases, such as obesity, diabetes, and dyslipidemia. We aimed to know the interactions of genetic variations of seven core circadian clock genes with lifestyle factors on the determination of metabolic parameters.

Methods: We have analyzed the impacts of genotype of seven core circadian clock genes (i.e., CLOCK, BMAL1, PER1, PER2, PER3, CRY1, and CRY2) and lifestyle factors (i.e., physical activity and sleep duration) in 575 Japanese males on the determination of metabolic parameters (i.e., body mass index [BMI], serum glucose, glycated hemoglobin [HbA1c], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C] levels).

Results: We have detected the associations between genotypes of PER3 and serum HbA1c level and genotypes of CRY1 and serum LDL-C level. Additionally, the interactions of the genotypes of PER1 and PER3 with physical activity for determining BMI, the genotypes of CLOCK with physical activity for determining serum HbA1c levels were observed. Furthermore, for determining serum HDL-C levels, the interactions of the genotypes of CRY2 with physical activity or sleep duration were observed.

Discussion/conclusion: Our findings indicate that the interactions of genotypes for core circadian clock genes and lifestyle factors (i.e., physical activity and sleep duration) are important for determining metabolic parameters.

Background: Arachidonic acid (ARA) is associated with colorectal cancer (CRC), a major public health concern. However, it is uncertain if ARA contributes to the development of colorectal polyps which are pre-malignant precursors of CRC.

Objective: The study aimed to investigate the association between lifelong exposure to elevated ARA and colorectal polyp incidence.

Methods: Summary-level GWAS data from European, Singaporean, and Chinese cohorts (n = 10,171) identified 4 single-nucleotide polymorphisms (SNPs) associated with blood ARA levels (p < 5 × 10-8). After pruning, 1 SNP was retained (rs174547; p = 3.0 × 10-971) for 2-stage Mendelian randomization.

Results: No association between ARA and colorectal polyp incidence was observed (OR = 1.00; 95% CI: 0.99, 1.00; p value = 0.50) within the UK Biobank (1,391 cases; 462,933 total).

Conclusions: Blood levels of ARA do not associate with colorectal polyp incidence in a general healthy population. Although not providing direct evidence, this work supports the contention that downstream lipid mediators, such as PGE2 rather than ARA itself, are key for polyp formation during early-stage colorectal carcinogenesis.

Introduction: The oral cavity is home to a diverse and distinct microbiome. While the role of oral bacteria in cariogenic and other dental diseases is irrefutable, their beneficial effects in the form of probiotics (PB) has been less studied, especially pertaining to oral diseases in children. This study compares the efficacy of a PB mouthrinse with 0.12% chlorhexidine (CHX) and 0.05% sodium fluoride (NaF) mouthrinse on the colony counts of mutans streptococci (MS) in children.

Methods: A triple-blind crossover randomized trial between interventional groups was planned. Fifty-one children between 8 to 12 years of age were divided into three groups (I, II, and III) and were exposed to all three mouthrinses (A, B, and C) by randomized allocation for a period of two weeks with an inter-phase washout period of four weeks. Pre- and post-interventional MS counts (CFU/mL) were assessed, and the mean change was analysed using the t test (intragroup) and ANOVA (intergroup and crossover).

Results: The mean changes in the colony counts obtained with the use of PB, CHX, and NaF mouthrinses were -1.0223 (-1.2201 to -0.8246), -0.9564 (-1.1503 to -0.7626), and -0.9511 (-1.1554 to -0.7467), respectively, which were statistically significant (p < 0.0001). However, the intergroup comparison for the mean change in colony counts revealed no statistically significant differences (p > 0.05).

Conclusion: The study concluded that the PB mouthrinse was equally efficacious as compared to CHX and NaF mouthrinses against MS in 8- to 12-year-old children. However, further studies are recommended to strengthen the evidence.

Introduction: Although many studies have investigated the association between smoking and obesity, very few have analyzed how obesity traits are affected by interactions between genetic factors and smoking. Here, we aimed to identify the loci that affect obesity traits via smoking status-related interactions in European samples.

Methods: We performed stratified analysis based on the smoking status using both the UK Biobank (UKB) data (N = 334,808) and the Genetic Investigation of ANthropometric Traits (GIANT) data (N = 210,323) to identify gene-smoking interaction for obesity traits. We divided the UKB subjects into two groups, current smokers and nonsmokers, based on the smoking status, and performed genome-wide association study (GWAS) for body mass index (BMI), waist circumference adjusted for BMI (WCadjBMI), and waist-hip ratio adjusted for BMI (WHRadjBMI) in each group. And then we carried out the meta-analysis using both GWAS summary statistics of UKB and GIANT for BMI, WCadjBMI, and WHRadjBMI and computed the stratified p values (pstratified) based on the differences between meta-analyzed estimated beta coefficients with standard errors in each group.

Results: We identified four genome-wide significant loci in interactions with the smoking status (pstratified < 5 × 10-8): rs336396 (INPP4B) and rs12899135 (near CHRNB4) for BMI, and rs998584 (near VEGFA) and rs6916318 (near RSPO3) for WHRadjBMI. Moreover, we annotated the biological functions of the SNPs using expression quantitative trait loci (eQTL) and GWAS databases, along with publications, which revealed possible mechanisms underlying the association between the smoking status-related genetic variants and obesity.

Conclusions: Our findings suggest that obesity traits can be modified by the smoking status via interactions with genetic variants through various biological pathways.

Introduction: Cataracts are associated with the accumulation of galactose and galactitol in the lens. We determined the polygenetic risk scores for the best model (PRSBM) associated with age-related cataract (ARC) risk and their interaction with diets and lifestyles in 40,262 Korean adults aged over 50 years belonging to a hospital-based city cohort.

Methods: The genetic variants for ARC risk were selected in lactose and galactose metabolism-related genes with multivariate logistic regression using PLINK 1.9 version. PRSBM from the selected genetic variants were estimated by generalized multifactor dimensionality reduction (GMDR) after adjusting for covariates. The interactions between the PRSBM and each lifestyle factor were determined to modulate ARC risk.

Results: The genetic variants for ARC risk related to lactose and galactose metabolism were SLC2A1_rs3729548, ST3GAL3_rs3791047, LCT_rs2304371, GALNT5_rs6728956, ST6GAL1_rs2268536, GALNT17_rs17058752, CSGALNACT1_rs1994788, GALNTL4_rs10831608, B4GALT6_rs1667288, and A4GALT_ rs9623659. In GMDR, the best model included all ten genetic variants. The highest odds ratio for a single SNP in the PRSBM was 1.26. However, subjects with a high-PRSBM had a higher ARC risk by 2.1-fold than a low-PRSBM after adjusting for covariates. Carbohydrate, dairy products, kimchi, and alcohol intake interacted with PRSBM for ARC risk, where participants with high-PRSBM had a much higher ARC risk than those with low-PRSBM when consuming diets with high carbohydrate and low dairy product and kimchi intake. However, only with low alcohol intake, the participants with high-PRSBM had a higher ARC risk than those with low-PRSBM.

Conclusion: Adults aged >50 years having high-PRSBM may modulate dietary habits to reduce ARC risk.