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Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease

BACKGROUND: In a genome-wide association scan, the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with increased liver fat content. We investigated whether this SNP is associated with the occurrence and progression of nonalcoho...

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Autores principales: Hotta, Kikuko, Yoneda, Masato, Hyogo, Hideyuki, Ochi, Hidenori, Mizusawa, Seiho, Ueno, Takato, Chayama, Kazuaki, Nakajima, Atsushi, Nakao, Kazuwa, Sekine, Akihiro
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018434/
https://www.ncbi.nlm.nih.gov/pubmed/21176169
http://dx.doi.org/10.1186/1471-2350-11-172
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author Hotta, Kikuko
Yoneda, Masato
Hyogo, Hideyuki
Ochi, Hidenori
Mizusawa, Seiho
Ueno, Takato
Chayama, Kazuaki
Nakajima, Atsushi
Nakao, Kazuwa
Sekine, Akihiro
author_facet Hotta, Kikuko
Yoneda, Masato
Hyogo, Hideyuki
Ochi, Hidenori
Mizusawa, Seiho
Ueno, Takato
Chayama, Kazuaki
Nakajima, Atsushi
Nakao, Kazuwa
Sekine, Akihiro
author_sort Hotta, Kikuko
collection PubMed
description BACKGROUND: In a genome-wide association scan, the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with increased liver fat content. We investigated whether this SNP is associated with the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) in the Japanese population. METHODS: SNP rs738409 was genotyped by the Taqman assay in 253 patients with NAFLD (189 with nonalcoholic steatohepatitis [NASH] and 64 with simple steatosis) and 578 control subjects. All patients with NAFLD underwent liver biopsy. Control subjects had no metabolic disorders. For a case-control study, the χ(2)-test (additive model) was performed. Odds ratios (ORs) were adjusted for age, gender, and body mass index (BMI) by using multiple logistic regression analysis with genotypes (additive model), age, gender, and BMI as the independent variables. Multiple linear regression analysis was performed to test the independent effect of risk allele on clinical parameters while considering the effects of other variables (age, gender, and BMI), which were assumed to be independent of the effect of the SNP. RESULTS: The risk allele (G-allele) frequency of rs738409 was 0.44 in the control subjects and 0.60 in patients with NAFLD; this shows a strong association with NAFLD (additive model, P = 9.4 × 10(-10)). The OR (95% confidence interval) adjusted for age, gender, and BMI was 1.73 (1.25-2.38). Multiple linear regression analysis indicated that the G-allele of rs738409 was significantly associated with increases in aspartate transaminase (AST) (P = 0.00013), alanine transaminase (ALT) (P = 9.1 × 10(-6)), and ferritin levels (P = 0.014), and the fibrosis stage (P = 0.011) in the patients with NAFLD, even after adjustment for age, gender, and BMI. The steatosis grade was not associated with rs738409. CONCLUSIONS: We found that in the Japanese population, individuals harboring the G-allele of rs738409 were susceptible to NAFLD, and that rs738409 was associated with plasma levels of ALT, AST, and ferritin, and the histological fibrosis stage. Our study suggests that PNPLA3 may be involved in the progression of fibrosis in NAFLD.
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spelling pubmed-30184342011-01-11 Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease Hotta, Kikuko Yoneda, Masato Hyogo, Hideyuki Ochi, Hidenori Mizusawa, Seiho Ueno, Takato Chayama, Kazuaki Nakajima, Atsushi Nakao, Kazuwa Sekine, Akihiro BMC Med Genet Research Article BACKGROUND: In a genome-wide association scan, the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with increased liver fat content. We investigated whether this SNP is associated with the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) in the Japanese population. METHODS: SNP rs738409 was genotyped by the Taqman assay in 253 patients with NAFLD (189 with nonalcoholic steatohepatitis [NASH] and 64 with simple steatosis) and 578 control subjects. All patients with NAFLD underwent liver biopsy. Control subjects had no metabolic disorders. For a case-control study, the χ(2)-test (additive model) was performed. Odds ratios (ORs) were adjusted for age, gender, and body mass index (BMI) by using multiple logistic regression analysis with genotypes (additive model), age, gender, and BMI as the independent variables. Multiple linear regression analysis was performed to test the independent effect of risk allele on clinical parameters while considering the effects of other variables (age, gender, and BMI), which were assumed to be independent of the effect of the SNP. RESULTS: The risk allele (G-allele) frequency of rs738409 was 0.44 in the control subjects and 0.60 in patients with NAFLD; this shows a strong association with NAFLD (additive model, P = 9.4 × 10(-10)). The OR (95% confidence interval) adjusted for age, gender, and BMI was 1.73 (1.25-2.38). Multiple linear regression analysis indicated that the G-allele of rs738409 was significantly associated with increases in aspartate transaminase (AST) (P = 0.00013), alanine transaminase (ALT) (P = 9.1 × 10(-6)), and ferritin levels (P = 0.014), and the fibrosis stage (P = 0.011) in the patients with NAFLD, even after adjustment for age, gender, and BMI. The steatosis grade was not associated with rs738409. CONCLUSIONS: We found that in the Japanese population, individuals harboring the G-allele of rs738409 were susceptible to NAFLD, and that rs738409 was associated with plasma levels of ALT, AST, and ferritin, and the histological fibrosis stage. Our study suggests that PNPLA3 may be involved in the progression of fibrosis in NAFLD. BioMed Central 2010-12-22 /pmc/articles/PMC3018434/ /pubmed/21176169 http://dx.doi.org/10.1186/1471-2350-11-172 Text en Copyright ©2010 Hotta et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hotta, Kikuko
Yoneda, Masato
Hyogo, Hideyuki
Ochi, Hidenori
Mizusawa, Seiho
Ueno, Takato
Chayama, Kazuaki
Nakajima, Atsushi
Nakao, Kazuwa
Sekine, Akihiro
Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease
title Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease
title_full Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease
title_fullStr Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease
title_full_unstemmed Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease
title_short Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease
title_sort association of the rs738409 polymorphism in pnpla3 with liver damage and the development of nonalcoholic fatty liver disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018434/
https://www.ncbi.nlm.nih.gov/pubmed/21176169
http://dx.doi.org/10.1186/1471-2350-11-172
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