PNPLA3 and metabolic syndrome: Some evidence also suggests that PNPLA3 and TM6SF2 gene variants may protect against cardiovascular risk, whereas variants in GCKR are associated with increased risk of cardiovascular disease, perhaps mediated by a decrease in the atherogenic dyslipidemia in both PNPLA3 and TM6SF2 carriers and an increase in the atherogenic dyslipidemia in GCKR carriers.139