Genetic background in nonalcoholic fatty liver disease: A comprehensive review

Table 3 Genes potentially involved in mechanisms of liver injury in nonalcoholic fatty liver disease evaluated by candidate gene studies

Gene	Functions of encoded protein	SNP
TNF-α, tumor necrosis factor-α	Proinflammatory cytokine also involved in the regulation of insulin resistance, release of free fatty acids, and apoptosis in hepatocytes	rs1800629
		rs361525
		rs1799964
		rs1800630
TRAIL, TNF-related apoptosis -inducing ligand	Protein functioning as a ligand that induces celluar apoptosis	rs6763816 rs4491934
IL-6, interleukin-6	Proinflammatory cytokine produced by adipocytes, hepatocytes, and immune cells also involved in the modulation of insulin resistance	rs1800795
IL-1β, interleukin-1β	Member of IL-1 family cytokine, mainly produced by adipose tissue	rs16944
TLR4, toll-like receptor 4	Receptor involved in the interaction with bacterial endotoxins capable to favor hepatic injury and a proinflammatory systemic status	rs4986790
IL28B, interleukin-28B	Cytokine belonging to the type III Interferon family	rs12979860
SOD2, superoxide dismutase 2	Manganese-dependent mitochondrial enzyme involved in protection from cellular injury induced by superoxide radicals	rs4880
CYP2E1, cytochrome P450 2E1	Part of the cytochrome P450 complex	rs2031920
UCP3, uncoupling protein 3	Mitochondrial anion carrier involved in the metabolism of superoxide radicals and in the modulation of lipid homeostasis	rs1800849 rs11235972
UCP2, uncoupling protein 2	Similar to uncoupling protein 3	rs695366
MTHFR, methylenetetrahydrofolate reductase	Enzyme involved in the methylation of homocysteine to methionine	rs1801133
		rs1801131
GCLC, Glutamate-cysteine ligase catalytic subunit	Limiting enzyme in the formation of glutathione, a relevant endogen antioxidant	rs17883901
HFE, hemochromatosis	Crucial protein for the regulation of iron homeostasis via the modulation of the expression of hepcidin	rs1800562
		rs1799945
TMPRSS6, trans-membrane protease serine 6	Matriptase-2, which cleaves the membrane-bound hemojuvelin, the co-receptor required for hepcidin expression in the liver	rs855791
KLF6, kruppel-like factor 6	One of the Kruppel-like factors, a family of transcriptional factors that regulate cellular proliferation, differentiation, and apoptosis	rs3750861
TGF-β1, transforming growth factor β1	In the liver, a promoter of hepatic fibrosis via the activation of hepatic stellate cells	rs1800471
ATII, angiotensin II	Part of the renin-angiotensin system, also advocated as an inducer of TGF-β1 production and accumulation of extracellular matrix in the liver	rs699
AGTR1, Angiotensin II Type 1 Receptor	Type 1 Receptor of Angiotensin II	rs3772622 rs3772633 rs2276736 rs3772630 rs3772627

SNP: Single nucleotide polymorphism; TGF: Transforming growth factor.