Preliminary additional analysis from this large cohort indicates that PNPLA3 GG carriers (8.2%) drink significantly less high percentage beverages (23% vs 55%, p < 0.001) but show no metabolic phenotype such as increased weight, BMI or diabetes.
PNPLA3 GG genotype carriers showed greater increases in the LFC and serum alanine aminotransferase (ALT) but lower PBG elevation and incident diabetes than PNPLA3 wild-type (CC) genotype carriers exhibiting the same degree of body weight increase.
Patients with NASH cirrhosis and cryptogenic cirrhosis were of a similar age and gender, as well as having a similar body mass index, PNPLA3rs738409 genotype, and prevalence of diabetes (p >0.05).
Logistic regression analysis showed that FINS, ADPN, HOMA-R, CPR, duration of diabetes mellitus and BMI had independently predictive value for diabetes complicated with CHD (P<0.05).
In conclusion, PNPLA3, and to a lesser extent, MBOAT7 variants are associated with NAFLD risk and modulate liver injury in non-obese patients without diabetes.
These data indicate that the liver expression of the PNPLA3 p.148M variant confers a genetic predisposition to liver graft steatosis along with nutritional status and diabetes.
When patients were grouped according to their diabetes status, the PNPLA3 genetic variants were associated with advanced liver fibrosis in diabetic patients only, but not in non-diabetic patients.
In the whole series combined, adiponutrin genotype was associated with steatosis grade >1 (OR = 1.35, 95% CI = 1.04-1.76), nonalcoholic steatohepatitis (OR = 1.5, 95% CI = 1.12-2.04), and fibrosis stage >1 (OR = 1.5, 95% CI = 1.09-2.12), independent of age, body mass index, and diabetes.