Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children

Larrieta‐Carrasco, Elena; León-Mimila, Paola; Villarreal-Molina, Teresa; Villamil‐Ramírez, Hugo; Romero‐Hidalgo, Sandra; Jacobo-Albavera, Leonor; Gutiérrez-Vidal, Roxana; López-Contreras, Blanca E.; Guillén-Pineda, Luz Elizabeth; Sánchez‐Muñoz, Fausto; Bojalil, Rafael; Mejía-Domínguez, Ana María; Méndez-Sánchez, Nahúm; Domínguez‐López, Aarón; Aguilar-Salinas, Carlos A.; Canizales‐Quinteros, Samuel

doi:10.1016/j.gene.2013.03.038

Cited by 35 publications

(22 citation statements)

References 33 publications

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“…Two PNPLA3 SNPs (rs3810622 and rs738409) were also associated with a greater risk of elevated ALT levels, but only in females. Our results support the association between PNPLA3 variant rs738409 (I148M) and elevated levels of ALT that has been observed in other studies with Mexican-Mestizo populations (Flores et al, 2016; Larrieta-Carrasco et al, 2014, 2013). The lack of significance among males could be due to the lower number of male participants in the MHWCS, as compared to females (70% vs. 30%, respectively) (Denova-Gutiérrez et al, 2016).…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, we also found that ALT and AST levels were significantly higher among the carriers of PNPLA3 variants rs3810622 and rs738409, and rs1227756 in COL13A1 , while rs2143571 in SAMM50 was only associated with increased levels of AST. The link between PNPLA3 rs738409 and higher ALT levels has been consistently replicated in different populations including Mexican adults, children, and Indigenous groups (Flores et al, 2016; Larrieta-Carrasco et al, 2014, 2013; León-Mimila et al, 2015). The effect of PNPLA3 rs3810622 on transaminase levels observed in our study is similar to the findings of GWAS studies with Japanese (Kitamoto et al, 2013) and Chinese populations (Song et al, 2016), although our results indicate a stronger and more significant association.…”

Section: Discussionmentioning

confidence: 85%

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Genetic variants in COL13A1, ADIPOQ and SAMM50 , in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population

Larrieta‐Carrasco

Flores

Macías-Kauffer

et al. 2018

Experimental and Molecular Pathology

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Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and risk of elevated transaminase levels in an admixed Mexican-Mestizo sample of 178 cases of NAFLD and 454 healthy controls. The rs2896019, rs12483959, and rs3810622 SNPs in PNPLA3 and rs1227756 in COL13A1 were associated with elevated alanine aminotransferase (ALT, ≥40 IU/L). A polygenic risk score (PRS) based on six SNPs in the ADIPOQ, COL13A1, PNPLA3, and SAMM50 genes was also associated with elevated ALT. Individuals carrying 9–12 risk alleles had 65.8% and 48.5% higher ALT and aspartate aminotransferase (AST) levels, respectively, than those with 1–4 risk alleles. The PRS showed the greatest risk of elevated ALT levels, with a higher level of significance than the individual variants. Our findings suggest a significant association between variants in COL13A1, ADIPOQ, SAMM50, and PNPLA3, and risk of NAFLD/elevated transaminase levels in Mexican adults with an admixed ancestry. This is the first study to examine high-density single nucleotide screening for genetic variations in a Mexican-Mestizo population. The extent of the effect of these variations on the development and progression of NAFLD in Latino populations requires further analysis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 85%

Genetic variants in COL13A1, ADIPOQ and SAMM50 , in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population

Larrieta‐Carrasco

Flores

Macías-Kauffer

et al. 2018

Experimental and Molecular Pathology

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“…Following a similar approach, Kawaguchi et al (91), demonstrated that the variant rs738409 of the patatin-like phospholipase domaincontaining 3/adiponutrin (PNPLA3) gene encoding an isoleucine to methionine substitution at amino acid position 148 leading to an inactivation of its triglyceride hydrolytic property, was strongly associated with the severity of NAFLD in Japanese subjects. This was confirmed in other studies performed in different groups or populations (92)(93)(94)(95).…”

Section: Future Developmentssupporting

confidence: 88%

Pediatric Nonalcoholic Fatty Liver Disease

Goran¹

2016

Childhood Obesity

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Summary:The rapidly increasing prevalence of childhood obesity and its associated co-morbidities such as hypertriglyceridemia, hyper-insulinemia, hypertension, early atherosclerosis, metabolic syndrome, and non-alcoholic fatty liver disease are major public health concerns in many countries. Therefore the trends in child and adolescent obesity should be closely monitored over time, as in the near future, we may anticipate a major increase of young adults with the stigmata of the metabolic syndrome, and of the related non-alcoholic fatty liver disease (NAFLD), that may lead to non-alcoholic steatohepatitis.

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“…After a strict process of literature retrieving and screening, we ultimately found 27 related studies that included 10 070 subjects from nine countries or regions. A workflow describing the literature retrieval process is shown in Figure .…”

Section: Resultsmentioning

confidence: 99%

Effect of the patatin‐like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta‐analysis of paediatric and adolescent individuals

Hua

Rui

et al. 2020

Pediatric Obesity

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Background: The effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of paediatric and adolescent nonalcoholic fatty liver disease (NAFLD) remains inconclusive.Objectives: We aimed to estimate the effect of this polymorphism not only on earlyonset NAFLD risk and severity but also on metabolic syndromes susceptibility.Methods: A systematic literature search was performed to identify relevant datasets.The odds ratio of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals were calculated to assess the strength of the associations.Results: Twenty-seven studies comprising 10 070 subjects were eligible. The summary effect showed that this polymorphism increased susceptibility to NAFLD development. Furthermore, it also indicated that nonalcoholic steatohepatitis (NASH) was more frequently observed in G allele carriers among paediatric and adolescent NAFLD patients. Moreover, the meta-analysis suggested that the variant was significantly associated with elevated liver damage indexes, including serum alanine transaminase, aspartate transaminase, gamma-glutamyltransferase concentrations, and liver fat content. However, the summary estimates for insulin resistance, lipid metabolism, and adiposity showed no significant associations. Conclusions:The PNPLA3 I148M polymorphism is associated with elevated earlyonset NAFLD risk, severity, and liver damage but not with related metabolic syndromes.

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Association of the I148M/PNPLA3 variant with elevated alanine transaminase levels in normal-weight and overweight/obese Mexican children

Cited by 35 publications

References 33 publications

Genetic variants in COL13A1, ADIPOQ and SAMM50 , in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population

Genetic variants in COL13A1, ADIPOQ and SAMM50 , in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population

Pediatric Nonalcoholic Fatty Liver Disease

Effect of the patatin‐like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta‐analysis of paediatric and adolescent individuals

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