NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features

doi:10.3390/biomedicines10112719

. 2022 Oct 27;10(11):2719.

doi: 10.3390/biomedicines10112719.

NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features

Affiliations

¹ Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, School of Medicine, University of Sao Paulo, Sao Paulo 048293, Brazil.
² Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, School of Medicine, University of São Paulo, Sao Paulo 048293, Brazil.
³ Division of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo, Sao Paulo 048293, Brazil.
⁴ Division of Gynecological Clinic, School of Medicine, University of Sao Paulo, Sao Paulo 048293, Brazil.
⁵ Institute of Tropical Medicine, LIM 07, University of Sao Paulo, Sao Paulo 048293, Brazil.

PMID: 36359239
PMCID: PMC9687705
DOI: 10.3390/biomedicines10112719

NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features

Amanda Medeiros Recuero et al. Biomedicines. 2022.

. 2022 Oct 27;10(11):2719.

doi: 10.3390/biomedicines10112719.

Authors

Affiliations

¹ Laboratório de Gastroenterologia Clínica e Experimental (LIM-07), Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, School of Medicine, University of Sao Paulo, Sao Paulo 048293, Brazil.
² Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, Hospital das Clínicas, School of Medicine, University of São Paulo, Sao Paulo 048293, Brazil.
³ Division of Endocrinology and Metabolism, School of Medicine, University of Sao Paulo, Sao Paulo 048293, Brazil.
⁴ Division of Gynecological Clinic, School of Medicine, University of Sao Paulo, Sao Paulo 048293, Brazil.
⁵ Institute of Tropical Medicine, LIM 07, University of Sao Paulo, Sao Paulo 048293, Brazil.

PMID: 36359239
PMCID: PMC9687705
DOI: 10.3390/biomedicines10112719

Abstract

Background: The aim of this study was to determine the frequency of the rs738409 polymorphism in the patatin-like phospholipase domain containing 3 (PNPLA3) gene in patients with polycystic ovary syndrome (PCOS) and its impact on nonalcoholic fatty liver disease (NAFLD) risk and severity. We also evaluated other risk factors associated with NAFLD and advanced fibrosis. Methods: This was a cross-sectional study involving 163 patients with PCOS at a tertiary center. Genotyping for the PNPLA3 polymorphism was undertaken using a TaqMan assay. The degree of fibrosis was defined by transient elastography. Results: The prevalence of NAFLD was 72.4%, and the polymorphism was heterozygous in 41.7% and homozygous in 8% of patients. Homeostasis model assessment of insulin resistance ≥ 2.5 was the main factor associated with the risk of developing NAFLD (OR = 4.313, p = 0.022), and its effect was amplified by the polymorphism (OR = 12.198, p = 0.017). Age > 32 years also conferred a higher risk for NAFLD. HDL values ≥ 50 mg/dL conferred protection against the outcome. Metabolic syndrome (OR = 13.030, p = 0.020) and AST > 32 U/L (OR = 9.039, p = 0.009) were independent risk factors for advanced fibrosis. Conclusions: In women with PCOS, metabolic characteristics are more relevant than PNPLA3 polymorphism regarding the risk for NAFLD and its advanced forms, but these factors can act synergistically, increasing disease risk.

Keywords: NAFLD; PCOS; insulin resistance; patatin-like phospholipase domain containing 3.

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Conflict of interest statement

None of the authors have any conflicts of interest.

Figures

**Figure 1**
Receiver operating characteristic (ROC) curve for clinical prediction model of NAFLD (A) and advanced fibrosis (B).

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[1] Chalasani N., Younossi Z., Lavine J.E., Diehl A.M., Brunt E.M., Cusi K., Charlton M., Sanyal A.J. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142:1592–1609. doi: 10.1053/j.gastro.2012.04.001. - DOI - PubMed

[2] Chalasani N., Younossi Z., Lavine J.E., Diehl A.M., Brunt E.M., Cusi K., Charlton M., Sanyal A.J. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142:1592–1609. doi: 10.1053/j.gastro.2012.04.001. - DOI - PubMed

[3] Younossi Z.M., Golabi P., de Avila L., Paik J.M., Srishord M., Fukui N., Qiu Y., Burns L., Afendy A., Nader F. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J. Hepatol. 2019;71:793–801. doi: 10.1016/j.jhep.2019.06.021. - DOI - PubMed

[4] Younossi Z.M., Golabi P., de Avila L., Paik J.M., Srishord M., Fukui N., Qiu Y., Burns L., Afendy A., Nader F. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J. Hepatol. 2019;71:793–801. doi: 10.1016/j.jhep.2019.06.021. - DOI - PubMed

[5] Romeo S., Kozlitina J., Xing C., Pertsemlidis A., Cox D., Pennacchio L.A., Boerwinkle E., Cohen J.C., Hobbs H.H. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 2008;40:1461–1465. doi: 10.1038/ng.257. - DOI - PMC - PubMed

[6] Romeo S., Kozlitina J., Xing C., Pertsemlidis A., Cox D., Pennacchio L.A., Boerwinkle E., Cohen J.C., Hobbs H.H. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 2008;40:1461–1465. doi: 10.1038/ng.257. - DOI - PMC - PubMed

[7] Tai C.M., Huang C.K., Tu H.P., Hwang J.C., Yeh M.L., Huang C.F., Huang J.F., Dai C.Y., Chuang W.L., Yu M.L. Interactions of a PPARGC1A Variant and a PNPLA3 Variant Affect Nonalcoholic Steatohepatitis in Severely Obese Taiwanese Patients. Medicine. 2016;95:e3120. doi: 10.1097/MD.0000000000003120. - DOI - PMC - PubMed

[8] Tai C.M., Huang C.K., Tu H.P., Hwang J.C., Yeh M.L., Huang C.F., Huang J.F., Dai C.Y., Chuang W.L., Yu M.L. Interactions of a PPARGC1A Variant and a PNPLA3 Variant Affect Nonalcoholic Steatohepatitis in Severely Obese Taiwanese Patients. Medicine. 2016;95:e3120. doi: 10.1097/MD.0000000000003120. - DOI - PMC - PubMed

[9] Sookoian S., Castaño G.O., Burgueño A.L., Gianotti T.F., Rosselli M.S., Pirola C.J. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J. Lipid Res. 2009;50:2111–2116. doi: 10.1194/jlr.P900013-JLR200. - DOI - PMC - PubMed

[10] Sookoian S., Castaño G.O., Burgueño A.L., Gianotti T.F., Rosselli M.S., Pirola C.J. A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity. J. Lipid Res. 2009;50:2111–2116. doi: 10.1194/jlr.P900013-JLR200. - DOI - PMC - PubMed

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NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features

Affiliations

NAFLD in Polycystic Ovary Syndrome: Association with PNPLA3 and Metabolic Features

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

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