👤 Karani S Vimaleswaran

Genetic variations within the Lipoprotein Lipase (LPL) gene have been shown to influence the risk of cardiometabolic diseases. However, their associations with cardiometabolic disease-related markers remain underexplored in Arab Qatari populations. Hence, we examined the association between a genetic risk score (GRS) based on three LPL single nucleotide polymorphisms (SNPs) and cardiometabolic indicators in a healthy Qatari population. A cross-sectional genetic association study was conducted using data from the Qatar Biobank population-based cohort, involving a sample of metabolically healthy Qatari adults (n = 6,919). The LPL-GRS was computed as the unweighted sum of risk alleles from three LPL SNPs: rs295 (C/A), rs301 (C/T), and rs320 (G/T). Associations between the GRS and metabolic markers were assessed using a generalized linear model, adjusting for age, sex, and body mass index. Individuals with high GRS (>5 risk alleles) showed a significant association with lower fat-free mass index values (β = -0.064, p = 0.029). In addition, a positive association was observed between GRS and fasting insulin levels (β = 0.035, p = 0.016). In addition, high GRS was significantly associated with lower high-density lipoprotein cholesterol (β = -0.025, p = 0.001) and higher triacylglycerol concentrations (β = 0.027, p = 0.0003) and systolic blood pressure (β = 0.007, p = 0.002), respectively. Our study shows that the LPL-GRS is associated with key cardiometabolic risk factors in this self-reported healthy Qatari population. These findings highlight the need for additional research to replicate these findings in independent and ethnically diverse cohorts, as well as the use of longitudinal studies to evaluate the predictive value of the GRS for future metabolic outcomes. Show less

Metabolic diseases, like type 2 diabetes mellitus and obesity, show a growing public health concern in Sri Lanka. Genetic predisposition and diet contribute to metabolic disease risk, but there are limited investigations into the impact of gene-diet interactions on metabolic disease risk in the Sri Lankan population. In this study, we examined whether a metabolic genetic risk score (GRS), constructed from 10 single nucleotide polymorphisms (SNPs), interacts with dietary factors to influence metabolic health indicators in Sri Lankan adults. This cross-sectional study included 105 generally healthy adults aged 25-50 years from the GOOD (Genetics of Obesity and Diabetes) study. Anthropometric, biochemical, and dietary data using food frequency questionnaires were collected using validated methods. Genotyping was performed using the KASP A statistically significant interaction was identified between the 10-SNP metabolic GRS and polyunsaturated fatty acid (PUFA) intake on waist circumference (P This study provides novel insights to understand gene-diet interactions affecting metabolic traits in Sri Lankans. The findings suggest that higher PUFA intake may mitigate genetic susceptibility to central obesity, highlighting the importance of personalized dietary recommendations for metabolic disease prevention. Further studies in larger cohorts are warranted to confirm this finding. Show less

The increased prevalence of metabolic diseases in the Arab countries is mainly associated with genetic susceptibility, lifestyle behaviours, such as physical inactivity, and an unhealthy diet. The objective of this review was to investigate and summarise the findings of the gene-lifestyle interaction studies on metabolic diseases such as obesity and type 2 diabetes in Arab populations. Relevant articles were retrieved from a literature search on PubMed, Web of Science, and Google Scholar starting at the earliest indexing date through to January 2024. Articles that reported an interaction between gene variants and diet or physical activity were included and excluded if no interaction was investigated or if they were conducted among a non-Arab population. In total, five articles were included in this review. To date, among three out of twenty-two Arab populations, fourteen interactions have been found between the Show less

Previous studies have pointed out a link between vitamin D status and metabolic traits, however, consistent evidence has not been provided yet. This cross-sectional study has used a nutrigenetic approach to investigate the interaction between metabolic-genetic risk score (GRS) and dietary intake on serum 25-hydroxyvitamin D [25(OH)D] concentrations in 396 unrelated Turkish adults, aged 24-50 years. Serum 25(OH)D concentration was significantly lower in those with a metabolic-GRS ≥ 1 risk allele than those with a metabolic-GRS < 1 risk allele ( Show less

Abnormalities in lipid metabolism have been linked to the development of obesity. We used a nutrigenetic approach to establish a link between lipids and obesity in Asian Indians, who are known to have a high prevalence of central obesity and dyslipidaemia. A sample of 497 Asian Indian individuals (260 with type 2 diabetes and 237 with normal glucose tolerance) (mean age: 44 ± 10 years) were randomly chosen from the Chennai Urban Rural Epidemiological Study (CURES). Dietary intake was assessed using a previously validated questionnaire. A genetic risk score (GRS) was constructed based on cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) genetic variants. There was a significant interaction between GRS and saturated fatty acid (SFA) intake on waist circumference (WC) (Pinteraction = 0.006). Individuals with a low SFA intake (≤23.2 g/day), despite carrying ≥2 risk alleles, had a smaller WC compared to individuals carrying <2 risk alleles (Beta = −0.01 cm; p = 0.03). For those individuals carrying ≥2 risk alleles, a high SFA intake (>23.2 g/day) was significantly associated with a larger WC than a low SFA intake (≤23.2 g/day) (Beta = 0.02 cm, p = 0.02). There were no significant interactions between GRS and other dietary factors on any of the measured outcomes. We conclude that a diet low in SFA might help reduce the genetic risk of central obesity confirmed by CETP and LPL genetic variants. Conversely, a high SFA diet increases the genetic risk of central obesity in Asian Indians. Show less

An abnormal lipid profile is considered a main risk factor for cardiovascular diseases and evidence suggests that single nucleotide polymorphisms (SNPs) in the cholesteryl ester transfer protein (CETP) gene contribute to variations in lipid levels in response to dietary intake. The objective of this review was to identify and discuss nutrigenetic studies assessing the interactions between CETP SNPs and dietary factors on blood lipids. Relevant articles were obtained through a literature search of PubMed and Google Scholar through to July 2021. An article was included if it examined an interaction between CETP SNPs and dietary factors on blood lipids. From 49 eligible nutrigenetic studies, 27 studies reported significant interactions between 8 CETP SNPs and 17 dietary factors on blood lipids in 18 ethnicities. The discrepancies in the study findings could be attributed to genetic heterogeneity, and differences in sample size, study design, lifestyle and measurement of dietary intake. The most extensively studied ethnicities were those of Caucasian populations and majority of the studies reported an interaction with dietary fat intake. The rs708272 (TaqIB) was the most widely studied CETP SNP, where 'B1' allele was associated with higher CETP activity, resulting in lower high-density lipoprotein cholesterol and higher serum triglycerides under the influence of high dietary fat intake. Overall, the findings suggest that CETP SNPs might alter blood lipid profiles by modifying responses to diet, but further large studies in multiple ethnic groups are warranted to identify individuals at risk of adverse lipid response to diet. Show less

This study aimed to explore the association between depression and body mass index (BMI), and to investigate whether genetic susceptibility to high BMI is different among individuals with or without depression. We used data on 251,125 individuals of white British ancestry from the UK Biobank. We conducted Mendelian randomization (MR) analysis to test for a causal association between depression and BMI using a major depressive disorder (MDD)-related genetic risk score (GRS We found observational and genetic evidence for an association between depression and BMI (MR beta: 0.09, 95% confidence interval [CI] 0.04-0.13). Further, the contribution of genetic risk to high BMI was higher among individuals with depression compared to controls. Carrying 10 additional BMI increasing alleles was associated with 0.24 standard deviation (SD; 95%CI 0.23-0.25) higher BMI among depressed individuals compared to 0.20 SD (95%CI 0.19-0.21) higher in controls, which corresponds to 3.4 kg and 2.8 kg extra weight for an individual of average height. Amongst the individual loci, the evidence for interaction was most notable for a variant near MC4R, a gene known to affect both appetite regulation and the hypothalamic-pituitary adrenal axis (p Genetic predisposition to high BMI was higher among depressed than to nondepressed individuals. This study provides support for a possible role of MC4R in the link between depression and obesity. Show less

We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were followed up for 6.9 ± 2.5 years. Association of 69 tagSNPs with baseline BMI and annual changes in weight as well as waist circumference were investigated using linear regression analysis. Interactions with sex, GI and intake of carbohydrates, fat as well as saturated, monounsaturated and polyunsaturated fatty acids were examined by including multiplicative SNP-covariate terms into the regression model. Neither baseline BMI nor annual weight or waist circumference changes were significantly associated with variation in the selected genes in the entire study population after correction for multiple testing. One SNP (rs1164) in LPIN2 appeared to be significantly interacting with sex (p = 0.0003) and was associated with greater annual weight gain in men (56.8 ± 23.7 g/year per allele, p = 0.02) than in women (-25.5 ± 19.8 g/year per allele, p = 0.2). With respect to gene-nutrient interaction, we could not detect any significant interactions when accounting for multiple testing. Therefore, out of our six candidate genes, LPIN2 may be considered as a candidate for further studies. Show less

Circulating levels of 25-hydroxyvitamin D (25OHD) are positively associated with high density lipoprotein (HDL) cholesterol. We sought to replicate a previously reported interaction between APOA5 genotype and vitamin D, and to examine whether HDL-associated genetic loci modify the association between serum 25OHD and HDL cholesterol. We examined whether 42 single nucleotide polymorphisms (SNPs) modify the association between serum 25OHD and HDL cholesterol in the 1958 British Birth cohort (aged 45 years, n = 4978). We identified a borderline interaction between the SNP rs12272004 (near the APOA5) and serum 25OHD on HDL cholesterol (P(interaction) = 0.05). The interaction was particularly prominent among the samples collected during winter (P(interaction) = 0.001). None of the other loci showed an interaction with serum 25OHD concentrations on HDL cholesterol. Our study in 4978 British Whites provides further support that APOA5 genotype modifies the association between vitamin D metabolites and HDL cholesterol. Show less

Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes. This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo. In total, 742 participants who had lost ≥ 8% of their initial body weight were randomly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein. The SNP main and SNP-diet interaction effects were analyzed by using linear regression models, corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile (Q-Q) plots. After correction for multiple testing, none of the SNPs were significantly associated with weight, waist circumference, or fat mass regain. Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo (-3.1 cm/allele; 95% CI: -4.6, -1.6; P/Bonferroni-corrected P = 0.000039/0.076), independently of diet. Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on waist circumference regain; in GHRL, CCK, MLXIPL, and LEPR on weight; in PPARC1A, PCK2, ALOX5AP, PYY, and ADRB3 on waist circumference; and in PPARD, FABP1, PLAUR, and LPIN1 on fat mass regain for dietary protein interaction. The observed effects of SNP-diet interactions on weight, waist, and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637. Show less