A genetic risk score is associated with hepatic triglyceride content and non-alcoholic steatohepatitis in Mexicans with morbid obesity

León-Mimila, Paola; Vega-Badillo, Joel; Gutiérrez-Vidal, Roxana; Villamil‐Ramírez, Hugo; Villareal-Molina, Teresa; Larrieta‐Carrasco, Elena; López-Contreras, Blanca E.; Kauffer, Luis R. Macías; Maldonado-Pintado, Diana Gabriela; Méndez-Sánchez, Nahúm; Tovar, Armando R.; Hernández-Pando, Rogelio; Velázquez‐Cruz, Rafael; Campos-Pérez, Francisco; Aguilar-Salinas, Carlos A.; Canizales‐Quinteros, Samuel

doi:10.1016/j.yexmp.2015.01.012

Cited by 57 publications

(54 citation statements)

References 43 publications

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“…Our findings suggest that among Mexicans, the PNPLA3 , LYPLAL1 , PPP1R3B , and GCKR polymorphisms may be associated with a greater risk of developing chronic liver disease in overweight/obese adults. Recently, a genetic risk score constructed with the PNPLA3 , LYPLAL1 , PPP1R3B , and GCKR polymorphisms was associated with a higher hepatic triglyceride content and ALT levels in Mexican Mestizo subjects with severe obesity [50]. Based on previously reported studies, our replication results suggest that the PNPLA3 , LYPLAL1 , PPP1R3B , and GCKR SNPs may be useful genetic markers to help identify sub-clinical liver disease among Mexicans who are overweight/obese.…”

Section: Discussionsupporting

confidence: 59%

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults

et al. 2016

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Purpose There is scarce information about the link between specific single-nucleotide polymorphisms (SNPs) and risk of liver disease among Latinos, despite the disproportionate burden of disease among this population. Our aim was to investigate nine SNPs in or near the following genes: PNPLA3, LYPLAL1, PPP1R3B, GCKR, NCAN, IRS1, PPARG, and ADIPOR2 and examine their association with persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels in Mexican adults. Materials and Methods Data and samples were collected from 741 participants in the Mexican Health Worker Cohort Study, in Cuernavaca, Mexico. We identified 207 cases who had persistently elevated levels of ALT or AST (≥40 U/L) and 534 controls with at least two consecutive normal ALT or AST results in a six month period, during 2006–2010 and 2011–2013. TaqMan assays were used to genotype the SNPs. Results and Discussion The risk allele of PNPLA3 rs738409 was found to be associated with persistently elevated levels of ALT or AST, adjusting for age, sex, BMI, type 2 diabetes, and ancestry: (OR = 2.28, 95% CI= 1.13, 4.58). A significant association was found between the LYPLAL1, PPP1R3B, and GCKR risk alleles and elevated ALT or AST levels among overweight/obese adults. Conclusion These results suggest that among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults. This study is the first to examine these nine SNPs in a sample of Mexican adults.

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Section: Discussionsupporting

confidence: 59%

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults

et al. 2016

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“…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%

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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“…As a common chronic liver disease, its spectrum ranged from simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis/cirrhosis and hepatocellular carcinoma [3, 4]. NAFLD is predicted to be the main course for liver disease world-wide by 2020 [5]. Epidemiologic studies showed a prevalence of about 20~30% in Western countries [6, 7] and 12~15% in China depending on population and investigative methods [8], which was similar to some previous studies [9–11].…”

Section: Introductionmentioning

confidence: 99%

Role of NCAN rs2228603 polymorphism in the incidence of nonalcoholic fatty liver disease: a case-control study

Yuan

Lu³

et al. 2016

Lipids Health Dis

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BackgroundRecently genome-wide association studies identified that NCAN rs2228603 polymorphism was associated with non-alcoholic fatty liver disease (NAFLD) mainly in subjects of European ancestry. While no research have been conducted to demonstrate the relationship between NCAN rs2228603 and NAFLD in Chinese Han adults. The aim of this study was to investigate whether NCAN rs2228603 is associated with NAFLD in Chinese population.MethodsGene NCAN rs2228603 was genotyped in 182 patients with NAFLD and 195 healthy controls. The expression of NCAN was tested according to polymerase chain reaction analysis (PCR) and serum lipids were performed by biology techniques.ResultsNo significant difference was found in genotype and allele frequencies of NCAN rs2228603 between the NAFLD group and the controls (P > 0.05). Subjects with the NCAN rs2228603 CT genotype showed a higher level of alkaline phosphatase (AKP) (P = 0.017) and a higher high-density lipoprotein (HDL) (P < 0.05).ConclusionsOur study for the first time identified that the gene NCAN rs2228603 is not a risk factor for the incidence of NAFLD in Chinese population. Also we found the dual and opposite role of T variant in protecting liver with a higher level of HDL and conferring risk for liver damage with a higher level of AKP.Trial registrationChinese Clinical Trial Register.gov Identifier: ChiCTR-ROC-15006447.

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A genetic risk score is associated with hepatic triglyceride content and non-alcoholic steatohepatitis in Mexicans with morbid obesity

Cited by 57 publications

References 43 publications

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults

Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults

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

Role of NCAN rs2228603 polymorphism in the incidence of nonalcoholic fatty liver disease: a case-control study

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