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Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals.
Am J Clin Nutr 2014; 99(4):869-74AJ

Abstract

BACKGROUND

A genome-wide association study identified variants in or near patatin-like phospholipase domain-containing-3 (PNPLA3), neurocan (NCAN), lysophospholipase-like 1 (LYPLAL1), glucokinase regulatory protein (GCKR), and protein phosphatase 1 regulatory subunit 3b (PPP1R3B) that were strongly associated with nonalcoholic fatty liver disease (NAFLD) in adults of European ancestry.

OBJECTIVE

We examined these genetic variants in obese children and tested whether their effects on NAFLD are significant in the Taiwanese Han Chinese population.

DESIGN

We genotyped PNPLA3 rs738409, NCAN rs2228603, LYPLAL1 rs12137855, GCKR rs780094, and PPP1R3B rs4240624 in 797 obese children aged 7-18 y. NAFLD was identified by liver ultrasonography. We analyzed the effect of these genetic variants on NAFLD.

RESULTS

NAFLD was identified in 24% of the recruited obese children. We found significant associations with NAFLD at variants in PNPLA3 and GCKR but not in NCAN, LYPLAL1, and PPP1R3B. Multiple logistic regression analysis showed that, after control for the effects of age- and sex-adjusted body mass index, waist-to-hip ratio, sex, and PNPLA3 rs738409 polymorphism, the variant GCKR rs780094 TT genotype independently increased the OR of NAFLD by 1.997 (95% CI: 1.196, 3.335; P = 0.008) compared with the CC genotype. Subjects with the variant GCKR rs780094 TT genotype had a higher mean serum alanine aminotransferase concentration than did those with the CC genotype (30.8 ± 34.7 compared with 22.2 ± 18.6 IU/L; P = 0.01).

CONCLUSIONS

By studying the genetic variants of obese Taiwanese children, we confirmed that the genetic variants in GCKR rs780094 and PNPLA3 rs738409, but not in NCAN rs2228603, LYPLAL1 rs12137855, and PPP1R3B rs4240624, are associated with an increased risk of NAFLD. GCKR and PNPLA3 variants are the common genetic factors that may confer susceptibility to NAFLD in obese individuals across multiple ethnic groups.

Authors+Show Affiliations

Department of Pediatrics, Far Eastern Memorial Hospital, Taipei, Taiwan (Y-CL and P-FC); the Departments of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan (M-HC and Y-HN); and the Oriental Institute of Technology, New Taipei City, Taiwan (Y-CL).No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24477042

Citation

Lin, Yu-Cheng, et al. "Genetic Variants in GCKR and PNPLA3 Confer Susceptibility to Nonalcoholic Fatty Liver Disease in Obese Individuals." The American Journal of Clinical Nutrition, vol. 99, no. 4, 2014, pp. 869-74.
Lin YC, Chang PF, Chang MH, et al. Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals. Am J Clin Nutr. 2014;99(4):869-74.
Lin, Y. C., Chang, P. F., Chang, M. H., & Ni, Y. H. (2014). Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals. The American Journal of Clinical Nutrition, 99(4), pp. 869-74. doi:10.3945/ajcn.113.079749.
Lin YC, et al. Genetic Variants in GCKR and PNPLA3 Confer Susceptibility to Nonalcoholic Fatty Liver Disease in Obese Individuals. Am J Clin Nutr. 2014;99(4):869-74. PubMed PMID: 24477042.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals. AU - Lin,Yu-Cheng, AU - Chang,Pi-Feng, AU - Chang,Mei-Hwei, AU - Ni,Yen-Hsuan, Y1 - 2014/01/29/ PY - 2014/1/31/entrez PY - 2014/1/31/pubmed PY - 2014/5/23/medline SP - 869 EP - 74 JF - The American journal of clinical nutrition JO - Am. J. Clin. Nutr. VL - 99 IS - 4 N2 - BACKGROUND: A genome-wide association study identified variants in or near patatin-like phospholipase domain-containing-3 (PNPLA3), neurocan (NCAN), lysophospholipase-like 1 (LYPLAL1), glucokinase regulatory protein (GCKR), and protein phosphatase 1 regulatory subunit 3b (PPP1R3B) that were strongly associated with nonalcoholic fatty liver disease (NAFLD) in adults of European ancestry. OBJECTIVE: We examined these genetic variants in obese children and tested whether their effects on NAFLD are significant in the Taiwanese Han Chinese population. DESIGN: We genotyped PNPLA3 rs738409, NCAN rs2228603, LYPLAL1 rs12137855, GCKR rs780094, and PPP1R3B rs4240624 in 797 obese children aged 7-18 y. NAFLD was identified by liver ultrasonography. We analyzed the effect of these genetic variants on NAFLD. RESULTS: NAFLD was identified in 24% of the recruited obese children. We found significant associations with NAFLD at variants in PNPLA3 and GCKR but not in NCAN, LYPLAL1, and PPP1R3B. Multiple logistic regression analysis showed that, after control for the effects of age- and sex-adjusted body mass index, waist-to-hip ratio, sex, and PNPLA3 rs738409 polymorphism, the variant GCKR rs780094 TT genotype independently increased the OR of NAFLD by 1.997 (95% CI: 1.196, 3.335; P = 0.008) compared with the CC genotype. Subjects with the variant GCKR rs780094 TT genotype had a higher mean serum alanine aminotransferase concentration than did those with the CC genotype (30.8 ± 34.7 compared with 22.2 ± 18.6 IU/L; P = 0.01). CONCLUSIONS: By studying the genetic variants of obese Taiwanese children, we confirmed that the genetic variants in GCKR rs780094 and PNPLA3 rs738409, but not in NCAN rs2228603, LYPLAL1 rs12137855, and PPP1R3B rs4240624, are associated with an increased risk of NAFLD. GCKR and PNPLA3 variants are the common genetic factors that may confer susceptibility to NAFLD in obese individuals across multiple ethnic groups. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/24477042/Genetic_variants_in_GCKR_and_PNPLA3_confer_susceptibility_to_nonalcoholic_fatty_liver_disease_in_obese_individuals_ L2 - https://academic.oup.com/ajcn/article-lookup/doi/10.3945/ajcn.113.079749 DB - PRIME DP - Unbound Medicine ER -