ASSOCIATION OF PNPLA3 (rs738409) AND GCKR (rs1260326) GENE POLYMORPHISMS WITH THE DEVELOPMENT OF NONALCOHOLIC FATTY LIVER DISEASE IN OBESE EGYPTIAN CHILDREN
Abstract
Non-Alcoholic fatty liver disease (NAFLD) is known as a common public health problem worldwide. Genetic variant as well as environmental factor interact to develop NAFLD. The allele frequency of PNPLA3 and GCKR variant varied in different ethnic groups. Our study aimed to recognize the association of the PNPLA3 rs738409 and GCKR rs1260326 with the occurrence and progression of NAFLD in obese Egyptian children. PNPLA3 rs738409 and GCKR rs1260326 were genotyped using RFLPPCR in 80 patients with NAFLD (40 with NAFL and 40 with non-alcoholic steatohepatitis [NASH]) and 80 control subjects. Comparison was made between NAFLD and control as well as between NAFL and NASH. The risk allele (G) allele frequency of PNPLA3 rs738409 was 0.456 in patients and 0.363 in control. Whereas, the risk allele (T) allele frequency of GCKR rs1260326 was 0.488 in patients and 0.331 in control. These two alleles show highly association with NAFLD (P = 0.00). Comparison between NAFL and NASH revealed that the frequencies of the (G) allele in PNPLA3 rs738409 were 0.3875, 0.5 in NAFL and NASH, respectively. Moreover, the allele frequencies of the (T) allele in GCKR rs1260326 were 0.413 and 0.575 in NAFL and NASH, respectively. Our findings demonstrate that both SNPs were highly associated with NASH. It is concluded that the PNPLA3 rs738409 and GCKR rs1260326 may have an important role in the development of NAFLD in obese Egyptian Children.References
Alyavi, A. L., G. N. Sobirova and M. M. Karimov (2014). Association of rs738409 polymorphism in the PNPLA3 gene with nonalcoholic fatty liver disease. International Journal of BioMedicine, 4: (Suppl 1) S8-S11.
Aragones, G., T. Auguet, S. Armengol, A. Berlanga, E. Guiu-Jurado, C. Aguilar, S. Martínez, F. Sabench, J. A. Porras, M. D. Ruiz, M. Hernández, J. J. Sirvent, D. Del Castillo and C. Richart (2016). PNPLA3 expression is related to liver steatosis in morbidly obese women with non-alcoholic fatty liver disease. Int. J. Mol. Sci., 17: pii: E630.
El-Koofy, N. M., H. M. El-Karaksy, I. M. Mandour, G. M. Anwar, M. S. El- Raziky and A. M. El-Hennawy (2011). Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children. Saudi J. Gastroenterol, 17: 265-270.
Hotta, K., M. Yoneda, H. Hyogo, H. Ochi, S. Mizusawa, T. Ueno, K. Chayama, A. Nakajima, K. Nakao and A. Sekine (2010). Association of the rs738409 polymorphism in PNPLA3 with liver damage and the development of nonalcoholic fatty liver disease. BMC Medical Genetics, 11: 172.
Li, X. L., J. Q. Sui, L. L. Lu, N. N. Zhang, X. Xu, Q. Y. Dong, Y. N. Xin and S. Y. Xuan (2016). Gene polymorphisms associated with nonalcoholic fatty liver disease and coronary artery disease: a concise review. Lipids in Health and Disease, 15: 53.
Lin, Y. C., P. F. Chang, M. H. Chang and Y. H. Ni (2014). Genetic variants in GCKR and PNPLA3 confer susceptibility to nonalcoholic fatty liver disease in obese individuals. Am. J. Clin. Nutr., 99: 869-874.
Manti, S., C. Romano, V. Chirico, M. Filippelli, C. Cuppari, I. Loddo, C. Salpietro and T. Arrigo (2014). Nonalcoholic fatty liver disease/ non-alcoholic steato-hepatitis in childhood: Endocrine-Metabolic “Mal-Programming”. Hepat., 14: el17641.
Marzuillo, P., E. Del Giudice and N. Santoro (2014). Pediatric fatty liver disease: role of ethnicity and genetics. World J. Gastroenterol, 20: 7347-7355.
Molleston, J. P., J. B. Schwimmer, K. P. Yates, K. F. Murray, O. W. Cummings, J. E. Lavine, E. M. Brunt, A. O. Scheimann, A. Unalp-Arida and NASH Clinical Research Network. (2014). Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels. J. Pediatr., 164: 707-713e3.
Palmer, N. D., S. K. Musani, L. M. Yerges-Armstrong, M. F. Feitosa, L. F. Bielak, R. Hernaez, B. Kahali, J. J. Carr, T. B. Harris, M. A. Jhun, S. L. R. Kardia, C. D. Langefeld, T. H. Mosley, J. M. Norris, A. V. Smith, H. A. Taylor, L. E. Wagenknecht, J. Liu, I. B. Borecki, P. Peyser and E. K. Speliotes (2013). Characterization of European ancestry nonalcoholic fatty liver disease-associated variants in individuals of African and hispanic descent. Hepatology, 58: 966-975.
Santoro, N., C. K. Zhang, H. Zhao, A. J. Pakstis, G. Kim, R. Kursawe, D. J. Dykas, A. E. Bale, C. Giannini, B. Pierpont, M. M. Shaw, L. Groop and S. Caprio (2012). Variant in the glucokinase regulatory protein (GCKR) gene is associated with fatty liver in obese children and adolescents. Hepatology, 55: 781- 789.
Sookoian, S. and C. J. Pirola (2017). Genetic predisposition in nonalcoholic fatty liver disease. Clin. Mol. Hepatology, 23: 1-12.
Sun, M. Y., L. Zhang, S. L. Shi and J. N. Lin (2016). Associations between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and non-alcoholic fatty liver disease (NAFLD) risk: a metaanalysis. PLoS ONE, 11: e0154337.
Zhang, L., W. You, H. Zhang, R. Peng, Q. Zhu, A. Yao, X. Li, Y. Zhou, X. Wang, L. Pu and J. Wu (2015). PNPLA3 polymorphisms (rs738409) and non-alcoholic fatty liver disease risk and related phenotypes: a meta-analysis. J. Gastroenterol Hepatology, 30: 821- 829.
