Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review

Table 1 Genes and variants emphasized in this review

Gene name	Genetic variant	Coding DNA change	Amino acid change	Putative effect of variant
PNPLA3	rs738409	444C>G	I148M	Increased hepatocyte triglyceride content
	rs6006460	1531G>T	S453I	Lower-than-average hepatic triglyceride accumulation
TM6SF2	rs58542926	499A>G	E167K	Elevated AST/ALT, increased hepatic triglyceride levels, decreased serum cholesterol
	rs10401969	613+80A>G	Intron	Lower hepatic TM6SF2 mRNA levels correlate with larger hepatocellular lipid droplets
LIPA	rs116928232	894G>A	E8SJM	Cholesterol ester storage disease often resulting in fibrosis→cirrhosis
IFNλ4	rs12979860	151-152G>A	Intron	Increased degree of hepatic inflammation and fibrosis
HFE	rs1800562	845G>A	C282Y	Increased hepatic iron uptake, associated with greater NAFLD risk/severity
	rs1799945	187C>G	H63D	Increased hepatic iron uptake, associated with greater NAFLD risk/severity
HMOX1	rs2071746	-413A>T	Affects promoter	Higher HMOX1 activity correlated with less frequent and less severe NAFLD
FTO	rs1421085	46-43098T>C	Affects repressor	Adipocytic phenotype shift from beige (energy-dissipating) to white (energy-storing)
GNPAT	rs11558492	1556A>G	D519G	Worsened iron overload in patients with HFE