Assessing Interactions between PNPLA3 and Dietary Intake on Liver Steatosis in Mexican-Origin Adults

Morrill, Kristin E.; Bland, Victoria L.; Klimentidis, Yann C.; Hingle, Melanie; Thomson, Cynthia A.; Garcia, David O.

doi:10.3390/ijerph18137055

Cited by 5 publications

(5 citation statements)

References 51 publications

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“…On the other hand, a randomized controlled trial in Latino youth with obesity did not find any significant association between liver outcomes and reducing dietary intake of sugar [49]. These findings go in line with those of Morrill et al, who did not find any significant association between level of hepatic steatosis and overall intake of carbohydrate, total sugar, added sugar, or fructose [50].…”

Section: Interaction Pnpla3-carbohydratessupporting

confidence: 82%

“…As with essential fatty acids, the consumption of simple sugars has also been studied in relation to steatosis, and there are still many contradictory results [46,[48][49][50][51][52]. There is mixed evidence on the effects of dietary carbohydrates on liver outcomes, but it was suggested that dietary patterns, including intake of sweetened beverages and vegetables, may interact with the PNPLA3 rs738409 variant to influence the severity of steatosis [46,48,51,52].…”

Section: Interaction Pnpla3-carbohydratesmentioning

confidence: 99%

“…However, the results of studies examining these effects are mixed. Some studies have found that high intake of sweetened beverages and high carbohydrate intake may worsen the reduced capacity of these individuals to hydrolyze triglycerides in the liver, leading to increased liver fat [46,48,51,52], while others have found no significant association between level of hepatic steatosis and overall carbohydrate, total sugar, added sugar, or fructose intake [49,50].…”

Section: Interaction Pnpla3-carbohydratesmentioning

confidence: 99%

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Nutritional Genomics in Nonalcoholic Fatty Liver Disease

et al. 2023

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Nonalcoholic fatty liver disease (NAFLD) is a common chronic condition associated with genetic and environmental factors in which fat abnormally accumulates in the liver. NAFLD is epidemiologically associated with obesity, type 2 diabetes, and dyslipidemia. Environmental factors, such as physical inactivity and an unbalanced diet, interact with genetic factors, such as epigenetic mechanisms and polymorphisms for the genesis and development of the condition. Different genetic polymorphisms seem to be involved in this context, including variants in PNPLA3, TM6SF2, PEMT, and CHDH genes, playing a role in the disease’s susceptibility, development, and severity. From carbohydrate intake and weight loss to omega-3 supplementation and caloric restriction, different dietary and nutritional factors appear to be involved in controlling the onset and progression of NAFLD conditions influencing metabolism, gene, and protein expression. The polygenic risk score represents a sum of trait-associated alleles carried by an individual and seems to be associated with NAFLD outcomes depending on the dietary context. Understanding the exact extent to which lifestyle interventions and genetic predispositions can play a role in the prevention and management of NAFLD can be crucial for the establishment of a personalized and integrative approach to patients.

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Section: Interaction Pnpla3-carbohydratessupporting

confidence: 82%

Section: Interaction Pnpla3-carbohydratesmentioning

confidence: 99%

Section: Interaction Pnpla3-carbohydratesmentioning

confidence: 99%

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Nutritional Genomics in Nonalcoholic Fatty Liver Disease

et al. 2023

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“…The rs738409 C>G mutation induce NAFLD by allowing the accumulation of PNPLA3 protein at the surface of hepatic lipid droplets, thus inhibiting the activity of local lipases and limiting the binding of the substrate to the catalytic site, and therefore impairing the triglycerides mobilization and hydrolysis in liver cells, resulting in the accumulation of triglycerides in the liver and causing the occurrence of fatty liver. The transcriptional up-regulation of PNPLA3 that occurs during carbohydrate loading may exacerbate the effect of the variant by increasing PNPLA3 protein production and consequently, rising triglyceride accumulation in the liver [35]. No association between PNPLA3 gene polymorphism rs738409 and degrees of steatosis or fibrosis was noted in our study.…”

Section: Genetic Analysiscontrasting

confidence: 54%

Association between rs738409 and rs139051 SNPs of the PNPLA3 gene and the presence of NAFLD

et al. 2022

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Genetics and epi-genetic alterations trigger the development of non-alcoholic fatty liver disease (NAFLD). Patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene is known to be a key regulator of lipid metabolism in the liver and is expressed in both adipocytes and hepatocytes. The aim is to evaluate the association between two single nucleotide polymorphism (SNPs) of PNPLA3 gene and NAFLD, and their relation to the degree of hepatic steatosis and fibrosis. Eighty individuals were selected and divided into two groups according to ultrasound finding of steatosis; a test group of 40 patients with bright liver and a group of 40 healthy subjects with normal liver. Steatosis was quantified by controlled attenuation parameter (CAP). Fibrosis assessment was done by fibrosis-4 (FIB-4), NAFLD fibrosis score, Fast score and Fibroscan. Complete blood count, liver enzymes, fasting blood glucose, and lipid profile were performed. Genomic DNA was isolated from blood. rs738409 C>G SNP of the PNPLA3 gene was determined via PCR-RFLP while rs139051 (A>G) polymorphism of the PNPLA3 gene was detected using TaqMan genotyping assay. GG genotype was significantly related to the presence of NAFLD (P=0.043) while the homozygous wild type (CC) was the common genotype among healthy controls. There was a significant association between the presence of the G allele (46.3%) in the PNPLA3 (I148 M) polymorphism and the presence of NAFLD (P <0.001). However, rs139051 PNPLA3 AG genotype was the most frequent genotype in both patients with NAFLD (82.5%) and healthy controls (85%). No significant correlation was found between any of the variants of both genotypes and the degrees of both steatosis and fibrosis detected by CAP and Fibroscan respectively. In conclusion, PNPLA3 gene polymorphism rs738409 but not rs139051 is significantly associated with NAFLD patients with simple steatosis. This blood test could serve as a screening tool for simple steatosis which warrants earlier follow-up and further intensive therapies.

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“…Risk of NAFLD is further increased in MO adults by a greater frequency (up to 55%) of the rs738409 C/G variant in patatin-like phospholipase domain-containing 3 (PNPLA3), which confers a substantially greater susceptibility to NAFLD and HCC. (10,12,17) Estimates from a Mexican population suggests the frequency of the G risk allele is higher at 77%, including 54.5% for the GG genotype and 11% for the CC genotype. (18) This variant is reported to be the strongest common genetic variant associated with NAFLD severity and progression, accounting for 5.3% of total phenotypic variance.…”

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confidence: 99%

Nonalcoholic Fatty Liver Disease and Associated Risk Factors in a Community‐Based Sample of Mexican‐Origin Adults

et al. 2022

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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 (P interaction = 0.08). The estimated OR for an increase in BMI of 5 kg/m 2 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 (P interaction = 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. (Hepatology Communications 2022;6:1322-1335).N onalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome that is defined as steatosis affecting ≥5% of hepatocytes not caused by excess alcohol intake, hepatitis B or C, autoimmune hepatitis, iron overload, drugs, or toxins. (1)(2)(3) It is estimated to affect approximately 20% (64 million) of the United States (US) population each year, leading to annual medical costs exceeding $100 billion. (4) Although not all individuals with NAFLD progress to end-stage liver disease, nearly 30% are at greater risk for developing cirrhosis, portal hypertension, and hepatocellular carcinoma (HCC), making NAFLD an emerging risk factor for HCC that is projected to become the leading cause of

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Assessing Interactions between PNPLA3 and Dietary Intake on Liver Steatosis in Mexican-Origin Adults

Cited by 5 publications

References 51 publications

Nutritional Genomics in Nonalcoholic Fatty Liver Disease

Nutritional Genomics in Nonalcoholic Fatty Liver Disease

Association between rs738409 and rs139051 SNPs of the PNPLA3 gene and the presence of NAFLD

Nonalcoholic Fatty Liver Disease and Associated Risk Factors in a Community‐Based Sample of Mexican‐Origin Adults

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