A control population of mixed ethnicities showed that 9% of the subjects possessing the variant allele had detectable hepatic steatosis versus 0% of those possessing the wild-type genotype. The implications of these findings are 2-fold. First, APOC3 and plasma triglyceride concentrations appear

to be important in the development of hepatic steatosis, even in the absence of obesity. All patients possessing variant alleles for the APOC3 gene had markedly higher average hepatic triglyceride contents (7.5% ± 10.3% versus 1.5% ± 1.3%). In fat-tolerance ZD1839 research buy testing of a subgroup of variant-allele and wild-type individuals, variant-allele subjects were also found to have significantly higher levels of plasma triglyceride. Similarly, plasma triglyceride clearance was decreased in a subgroup of patients with the variant allele versus their wild-type counterparts. In all, this provides compelling evidence that APOC3 can contribute to triglyceride excess both intrahepatically and systemically. The BGJ398 purchase second and more novel finding of these authors is the genetic association between Asian Indian men and this polymorphism. This population has a high prevalence of NAFLD, and this is the first study to associate a specific genetic variation with hepatic steatosis in healthy men of Asian Indian descent. This finding was substantiated

in an independent group of non-Asian men, and the authors noted that no wild-type homozygotes at this allele were found to have hepatic steatosis by magnetic resonance spectroscopy. It is important to understand that the frequency of variant alleles was no greater in the Asian Indian study population versus the control group composed of multiple ethnicities, and this suggests that this APOC3 variant allele does not explain the high rates of hepatic steatosis among Asian Indians. Other genetic variations, such as that encoding the patatin-like phospholipase domain-containing

3 protein (PNPLA3), have also been independently associated with NAFLD,5 with recent research linking specific polymorphisms Vorinostat order to disease severity.6-8 In the study by Petersen etal.,3 PNPLA3 variants were also shown to be associated with NAFLD, and the relative risk appeared additive in those individuals having both PNPLA3 and APOC3 variants. However, only 13.1% of the variance in risk for NAFLD could be explained by the combination of these two different SNPs, and this suggests that additional factors may be involved in the development of NAFLD. The authors also selected seven subjects with hepatic steatosis and insulin resistance (IR) for enrollment in a 6-month weight-loss program; during this time, they experienced a mean weight loss of approximately 6 kg along with a significant reduction in their hepatic triglyceride content from 14.0% to 3.8% (P = 0.05) and an improvement in the insulin sensitivity index from 1.8 to 3.7 (P < 0.01).