Assessing Interactions between PNPLA3 and Dietary Intake on Liver Steatosis in Mexican-Origin Adults.
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SUBMITTER: Morrill KE
PROVIDER: S-EPMC8296936 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Introduction and objectivesVarious studies have identified single-nucleotide polymorphisms (SNPs) associated with nonalcoholic fatty liver disease (NAFLD) and related traits, including ones located in or near the LYPLAL1, GCKR, PPP1R3B, TM6SF2, MBOAT7, and PNPLA3 genes. However, these SNPs were identified primarily in populations of European ancestry. This study examined the associations of these previously identified SNPs with hepatic steatosis in a sample of Mexican-origin adults living in Southern Arizona.Materials and methodsA total of 307 Mexican-origin adults between the ages of 18 and 64 with a body mass index (BMI) of 25 kg/m2 or higher were genotyped at the following SNPs: rs12137855 (LYPLAL1), rs1260326 (GCKR), rs4240624 (PPP1R3B), rs58542926 (TM6SF2), rs641738 (MBOAT7), and rs738409 (PNPLA3). Hepatic steatosis was assessed by transient elastography (FibroScan®) with controlled attenuation parameter. Regression models examined the association between each of the six SNPs and hepatic steatosis. BMI was examined as a potential modifier of the genetic associations.ResultsParticipants were, on average, 45 years old and mostly female (63%) with an overall mean hepatic steatosis of 288.1 dB/m. Models showed no associations between LYPLAL1, GCKR, PPP1R3B, TM6SF2, or MBOAT7 and hepatic steatosis. Only PNPLA3 was statistically significantly associated with hepatic steatosis in both unadjusted and adjusted models (p<0.01). There was no effect modification observed with BMI.ConclusionsSNPs associated with NAFLD in populations of European descent did not strongly contribute to hepatic steatosis in individuals of Mexican-origin, except for rs738409 (PNPLA3). Further efforts are necessary to explore additional SNPs that may be associated with NAFLD in this high-risk population.
| S-EPMC10486257 | biostudies-literature
Project description:Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3's function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients.
| S-EPMC4465608 | biostudies-literature
Project description:PURPOSE:This study examined genetic associations of patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and liver aminotransferases in an extensively documented, randomly recruited Mexican American population at high risk of liver disease. METHODS:Two single nucleotide polymorphisms (SNP) in the PNPLA3 gene (i.e., rs738409 and rs2281135) were genotyped in 1532 individuals. Population stratification was corrected by the genotyping of 103 ancestry informative markers (AIMs) for Mexican Americans. RESULTS:Both PNPLA3 SNPs showed highly significant association with alanine aminotransferase (ALT) levels, but was also, in males, associated with aspartate aminotransferase (AST) levels. Haplotypic association test of the two SNPs suggested stronger genetic association with rs738409 than rs2281135. Obvious sex effects were observed: rs738409-sex interaction in ALT levels P = 8.37 x 10(-4); rs738409-sex interaction in AST levels P = 5.03 x 10(-3). CONCLUSIONS:This population study highlights a sex-specific association of PNPLA3 polymorphisms and elevated liver enzymes in a population-based study, independent of common pathological factors of the metabolic syndrome. The strong genetic association found in women ? 50 years old, but not in women > 50 years old, suggests that sex hormones may mediate the sex effect.
| S-EPMC3441048 | biostudies-literature
Project description:IntroductionThe burden of non-alcoholic fatty liver disease (NAFLD) continues to disproportionately impact under-resourced communities in the U.S., particularly Mexican-origin populations. Genetic polymorphisms such as the rs738409 C/G variant in patatin-like phospholipase domain-containing 3 (PNPLA3) have been associated with higher prevalence of and progression along the NAFLD spectrum. This qualitative study conducted in the U.S. Southwest aimed to assess Mexican-origin men's experience receiving genetic testing for PNPLA3 risk carrier status.MethodsSemi-structured interviews were conducted with 17 Mexican-origin men whose NAFLD status and genetic predisposition were determined as part of a previous cross-sectional study. The interview guide included questions exploring participants' insights on how genetic risk status was delivered, how the information influenced their motivation for lifestyle modification to reduce NAFLD risk, and any knowledge sharing that occurred with family members after learning of their PNPLA3 risk status. Interviews were conducted and audio recorded in English (n = 6) and Spanish (n = 11) and uploaded into NVivo software for data analysis and interpretation. Guided by the Health Belief Model, a thematic analysis approach was used to identify primary themes.ResultsResults highlighted men's preference for receiving this type of genetic risk information through a letter sent to their homes. General comprehension of PNPLA3 risk status was deemed high and most men stated sharing their genetic predisposition to NAFLD with their immediate family members. Participants also indicated that family and awareness of this genetic risk acted as primary motivators for implementing behavior changes (e.g., diet, physical activity) toward the prevention of more severe liver conditions.DiscussionFindings from this qualitative study suggest the feasibility of communicating genetic risk for NAFLD among Mexican-origin men. Future strategies for the dissemination of genetic risk results among Mexican-origin individuals should consider familial and cultural appropriate strategies.
| S-EPMC9846364 | biostudies-literature
Project description:Fructose intake has been associated with non-alcoholic fatty liver disease (NAFLD). The objective of this study was to assess the consumption of dietary fructose according to: 1) classification of hepatic steatosis by two indexes and 2) diagnosis of NAFLD by MRI. We conducted a cross-sectional analysis among 100 young adults from Mexico City. The Hepatic Steatosis Index (HSI) and the Fatty Liver Index (FLI) were estimated using Body Mass Index (BMI), waist circumference, and fasting concentrations of glucose, triglycerides, and hepatic enzymes (ALT, AST, GGT). A semi-quantitative food frequency questionnaire was administered to obtain dietary sources of fructose. We estimated the concordance between the hepatic indices and NAFLD and the correlation between the index scores and the percentage of liver fat. Eighteen percent presented NAFLD; 44% and 46% were classified with hepatic steatosis according to HSI and FLI, respectively. We compared dietary intake of fructose by each outcome: HSI, FLI, and NAFLD. Sugar-sweetened beverages (SSB) and juices were consumed significantly more by those with steatosis by FLI and NAFLD suggesting that SSB intake is linked to metabolic alterations that predict the risk of having NAFLD at a young age.
| S-EPMC6470703 | biostudies-literature
Project description:Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.
| S-EPMC4881456 | biostudies-literature
Project description:Evidence relating dietary patterns to obesity and related disorders such as non-alcoholic fatty liver disease (NAFLD) is limited in pediatric age. Aim of this study was to analyze the association between dietary patterns, obesity and development of severe steatosis and the metabolic syndrome in a series of children and adolescents referred for suspected NAFLD, and the interaction with the rs738409 I148M PNPLA3 polymorphism. Two hundred patients (112 females) had completed a food frequency and demographic questionnaire. Nearly 58 % were obese, and 32 % were overweight. Mild, moderate, and severe fatty liver was present in 60 (30 %), 87 (44 %), and 51 (26 %) participants, respectively. A great proportion of overweight/obese children and adolescents reported a correct dietary pattern. At multivariate ordinal regression analysis considering demographic, anthropometric, genetic, and behavioral determinants, the major determinant of steatosis severity was PNPLA3 I148M genotype (p < 0.0001), followed by older age (p = 0.017), higher waist circumference (p = 0.016), and less time spent practising physical exercise (p = 0.034). Furthermore, there was a significant interaction between PNPLA3 I148M and intake of sweetened beverages (p = 0.033) and of vegetables (p = 0.038). In conclusion, although dietary pattern was reportedly correct in at-risk overweight adolescents with NAFLD, we report a novel interaction between PNPLA3 I148M and dietary components with the severity of steatosis.
| S-EPMC4026440 | biostudies-literature
Project description:Background: Evidence on the association of non-alcoholic fatty liver disease (NAFLD), a public health concern, with dietary fiber intake is inconsistent. Objective: To investigate the relationship between dietary fiber intake from different sources and NAFLD risk in US adults. Methods: Data were collected from the 2007-2014 National Health and Nutrition Examination Survey. NAFLD was defined as a United States Fatty Liver Index ≥30, and dietary fiber intake was assessed through two 24-h dietary recall interviews. Logistic regression and restricted cubic spline models were used to explore the relationship of dietary intakes of total, cereal, fruit, and vegetable fiber with NAFLD risk. Results: A total of 6,613 participants, aged more than 20 years, were included in this study. After adjusting for multiple confounding factors, the odds ratios and 95% confidence intervals of NAFLD for the highest quartile vs. lowest quartile intakes of total, cereal, fruit, and vegetable fiber were 0.12 (0.08-0.16), 0.25 (0.19-0.33), 0.41 (0.33-0.52), and 0.42 (0.32-0.56), respectively. In stratified analyses by sex and age, statistically significant negative associations of dietary intakes of total, cereal, fruit, and vegetable fiber with NAFLD risk were observed in all participants. Dose-response analysis indicated a non-linear correlation between NAFLD risk and dietary intake of total fiber, whereas the relationship was linear for cereal, fruit, and vegetable fiber intakes. Conclusion: Total, cereal, fruit, and vegetable fiber intakes exhibit negative correlations with NAFLD risk in the general adult population in the United States.
| S-EPMC7710900 | biostudies-literature
Project description:The incidence of nonalcoholic fatty liver disease (NAFLD) is highest among Mexican-origin (MO) adults. Few studies have estimated the prevalence of NAFLD in this subpopulation, particularly by sex and age. We assessed the prevalence of NAFLD in a community sample of MO adults residing in a border region of southern Arizona and determined risk factors associated with NAFLD. A total of 307 MO adults (n = 194 women; n = 113 men) with overweight or obesity completed an in-person study visit, including vibration-controlled transient elastography (FibroScan) for the assessment of NAFLD status. A continuous attenuation parameter score of ≥288 dB/m (≥5% hepatic steatosis) indicated NAFLD status. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD. We identified 155 participants (50%) with NAFLD, including 52% of women and 48% of men; there were no sex differences in steatosis (men, 287.8 dB/m; women, 288.4 dB/m). Sex, age, patatin-like phospholipase domain containing 3 (PNPLA3) risk allele carrier status, comorbidities, and cultural and behavioral variables were not associated with NAFLD status. There was some evidence for effect modification of body mass index (BMI) by sex (Pinteraction = 0.08). The estimated OR for an increase in BMI of 5 kg/m2 was 3.36 (95% CI, 1.90, 5.91) for men and 1.92 (95% CI, 1.40, 2.64) for women. In post hoc analyses treating steatosis as a continuous variable in a linear regression, significant effect modification was found for BMI by sex (Pinteraction = 0.03), age (P = 0.05), and PNPLA3 risk allele carrier status (P = 0.02). Conclusion: Lifestyle interventions to reduce body weight, with consideration of age and genetic risk status, are needed to stem the higher rates of NAFLD observed for MO populations.
| S-EPMC9134817 | biostudies-literature
Project description:BackgroundObesity and diabetes mellitus (DM) are public health concerns in Mexico of top-level priority due to their high prevalence and their growth rate in recent decades. The accumulation of adipose tissue leads to an unbalanced release of pro-oxidant factors, which causes cellular damage and favors the development of comorbidities. Recent evidence suggests that oxidative stress also promotes the accumulation of adipose tissue and the development of insulin resistance. The objective of this study is to evaluate the association between usual intake of antioxidant nutrients, specifically vitamins A, C, E and magnesium with body mass index (BMI), waist circumference (WC) and serum glucose concentrations in a representative sample of Mexican adults.MethodologyWe analyzed data on diet, BMI, WC and serum glucose from the Mexican National Health and Nutrition Survey 2012. Analysis included 20- to 65-year-old adults without a known diagnosis of DM (n = 1573). Dietary information was obtained using the five-step multiple-pass method developed by the United States Department of Agriculture and adapted to the Mexican context. Nutrient usual intake distributions were estimated using the Iowa State University method, through the "Software for Intake Distribution Estimation" (PC-Side) v.1.02. Associations were analyzed using multivariate regression models.ResultsHigher dietary magnesium intake was associated with lower markers of adiposity, so that an increase in 10 mg per 1000 kcal/day of magnesium was associated with an average decrease in BMI of 0.72% (95% CI: -1.36, - 0.08) and 0.49 cm (95% CI: -0.92, - 0.07) of WC. Additionally, in women with normal glucose concentrations, an increase in magnesium intake was associated with an average decrease in serum glucose by 0.59% (95% CI: -1.08, - 0.09).ConclusionThe results suggest that magnesium intake is associated with lower BMI, WC and serum glucose in Mexican population. However, more studies are required to elucidate the nature of this association.
| S-EPMC6282375 | biostudies-literature