O-4 MBOAT7 RS641738 IS ASSOCIATED WITH PROGRESSION TO CIRRHOSIS IN NON-ALCOHOLIC FATTY LIVER DISEASE IN LATIN AMERICA

Introduction and Objectives

Latin Americans experience some of the highest global rates of non-alcoholic fatty liver disease (NAFLD) and the prevalence of cirrhosis is increasing in this population. The rs641738 C>T single nucleotide polymorphism (SNP) of MBOAT7 has been associated with NAFLD development and cirrhosis in Europeans with NAFLD. However, the impact of this SNP in Latin Americans is unclear. We aimed to evaluate a cohort of Latin Americans with NAFLD to determine if MBOAT7 effects the risk of cirrhosis in this understudied population.

Materials and Methods

Individuals with NAFLD from 6 South American countries (Argentina, Ecuador, Brazil, Chile, Peru and Colombia) were prospectively recruited via the ESCALON network. Genotyping was performed with the TaqMan-genotyping assay. Genotype frequencies for MBOAT7 were compared using chi-square. Those with hepatocellular carcinoma were excluded.

Results

A total of 278 patients were included, 189 with cirrhosis and 89 without cirrhosis. 55% of the cirrhosis cohort were females compared to 61% of the cohort without cirrhosis (p=0.337). The median ages of those with and without cirrhosis were 64 (IQR 59-70) and 60 years (IQR 52-65), respectively. The MBOAT7 TT genotype was present in 36/189 (19%) of subjects with cirrhosis and 7/89 (8%) of subjects without cirrhosis (OR=2.76, 95% CI: 1.17-6.47, p=0.016). We evaluated the minor allele frequency (MAF) of MBOAT7 in our cirrhosis cohort compared to the Latin American population in the gnomAD database, a genome database with 17,720 sequences belonging to Latin Americans. MAF was elevated in cirrhotics compared to the general Latin American population (43% vs. 33% respectively, OR=1.54, 95% CI: 1.25-1.89, p<0.001).

Conclusions

The rs641738 C>T SNP of MBOAT7 was associated with cirrhosis in a cohort of Latin Americans with NAFLD. Identification of genetic risk factors for liver disease may lead to improved risk stratification and interventional strategies in this population with an increasing burden of liver disease.