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Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease.
BMC Med Genet 2010; 11:172BM

Abstract

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 x 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 x 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.

Authors+Show Affiliations

EBM Research Center, Kyoto University Graduate School of Medicine, Japan. kikukoh@kuhp.kyoto-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21176169

Citation

Hotta, Kikuko, et al. "Association of the Rs738409 Polymorphism in PNPLA3 With Liver Damage and the Development of Nonalcoholic Fatty Liver Disease." BMC Medical Genetics, vol. 11, 2010, p. 172.
Hotta K, Yoneda M, Hyogo H, et al. Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease. BMC Med Genet. 2010;11:172.
Hotta, K., Yoneda, M., Hyogo, H., Ochi, H., Mizusawa, S., Ueno, T., ... Sekine, A. (2010). Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease. BMC Medical Genetics, 11, p. 172. doi:10.1186/1471-2350-11-172.
Hotta K, et al. Association of the Rs738409 Polymorphism in PNPLA3 With Liver Damage and the Development of Nonalcoholic Fatty Liver Disease. BMC Med Genet. 2010 Dec 22;11:172. PubMed PMID: 21176169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease. AU - Hotta,Kikuko, AU - Yoneda,Masato, AU - Hyogo,Hideyuki, AU - Ochi,Hidenori, AU - Mizusawa,Seiho, AU - Ueno,Takato, AU - Chayama,Kazuaki, AU - Nakajima,Atsushi, AU - Nakao,Kazuwa, AU - Sekine,Akhiro, Y1 - 2010/12/22/ PY - 2010/08/23/received PY - 2010/12/22/accepted PY - 2010/12/24/entrez PY - 2010/12/24/pubmed PY - 2012/10/30/medline SP - 172 EP - 172 JF - BMC medical genetics JO - BMC Med. Genet. VL - 11 N2 - 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 x 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 x 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. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/21176169/Association_of_the_rs738409_polymorphism_in_PNPLA3_with_liver_damage_and_the_development_of_nonalcoholic_fatty_liver_disease_ L2 - https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-11-172 DB - PRIME DP - Unbound Medicine ER -