Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 8, 2015; 7(10): 1433-1438
Published online Jun 8, 2015. doi: 10.4254/wjh.v7.i10.1433
Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal
Lourianne Nascimento Cavalcante, Jose Tadeu Stefano, Mariana V Machado, Daniel F Mazo, Fabiola Rabelo, Kiyoko Abe Sandes, Flair José Carrilho, Helena Cortez-Pinto, Andre Castro Lyra, Claudia P de Oliveira
Lourianne Nascimento Cavalcante, Andre Castro Lyra, Gastro-Hepatology Department, Hospital Sao Rafael, Salvador BA 41253-190, Brazil
Jose Tadeu Stefano, Daniel F Mazo, Fabiola Rabelo, Flair José Carrilho, Claudia P de Oliveira, Division of Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo SP 05469-000, Brazil
Mariana V Machado, Helena Cortez-Pinto, Department of Gastroenterology, Laboratory of Nutrition, University Hospital of Santa Maria University, 1649-035 Lisboa, Portugal
Kiyoko Abe Sandes, Life Sciences Department, University of Bahia State, Salvador BA 41253-190, Brazil
Andre Castro Lyra, Faculty of Medicine, Federal University of Bahia, Salvador BA 41253-190, Brazil
Author contributions: Cavalcante LN contributed to analysis and interpretation of the data, drafting of the article and revising for reviewers comments; Stefano JT, Cortez-Pinto H, Lyra AC and de Oliveira CP contributed to conception and design, critical revision of the article and data collection; Sandes KA and Carrilho FJ contributed to data collection; Machado MV, Mazo DF and Rabelo F contributed to treatment of patients and data collection; all authors approved the final version of the paper.
Ethics approval: Ethics Committees and Hospital Institutional Review Board from University of São Paulo School of Medicine and from the Hospital of Santa Maria University Lisbon have approved this study (Doc. No. 435.621, CAAE: 14399113.0.0000.0068).
Informed consent: All patients provided written informed consent before starting the study procedures.
Conflict-of-interest: All the authors have no conflicts of interests.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at email lourianne@gmail.com. All participants gave written informed consent for data sharing. Presented data were anonymized.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lourianne Nascimento Cavalcante, MD, Gastro-Hepatology Department, Hospital Sao Rafael, Av. São Rafael 2152, Salvador BA 41253-190, Brazil. lourianne@gmail.com
Telephone: +55-71-32816432 Fax: +55-71-32816855
Received: October 11, 2014
Peer-review started: October 13, 2014
First decision: October 28, 2014
Revised: December 1, 2014
Accepted: April 8, 2015
Article in press: April 9, 2015
Published online: June 8, 2015
Abstract

AIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal.

METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnic-geographical differential frequencies (≥ 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P < 0.05).

RESULTS: In the Brazilian sample, NASH was significantly more frequent among the elderly patients with diabetes (NASH 56 ± 1.1 years old vs S. Steatosis 51 ± 1.5 years old, P = 3.7 x 10-9), dyslipidemia (NASH 63% vs S. Steatosis 37%, P = 0.009), higher fasting glucose levels (NASH 124 ± 5.2 vs S. Steatosis 106 ± 5.3, P = 0.001) and Homeostatic Model of Assessment index > 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups.

CONCLUSION: There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort.

Keywords: Ancestry, Nonalcoholic fatty liver disease, Simple steatosis, Nonalcoholic steatohepatitis, Admixed population

Core tip: Nonalcoholic fatty liver disease (NAFLD) is frequent and may lead to cirrhosis and hepatocellular carcinoma. Awareness about its risk factors and predictive markers of severity is important in the management of this infirmity. Self-reported ancestry may also influence NAFLD outcomes in homogeneous populations and African descendants appear to have milder disease than Caucasians. However, there are no available data that demonstrate the relationship between ancestry and NAFLD in admixed populations. This is the first study to evaluate the possible association between ancestry analyzed for genetic markers and biopsy-proven NAFLD in a homogeneous and a highly admixed population.