Genetic background in nonalcoholic fatty liver disease: A comprehensive review

Table 2 Genes influencing glucidic or lipid metabolism with a potential role in nonalcoholic fatty liver disease pathogenesis evaluated by candidate gene studies

Gene	Functions of encoded protein	SNP
ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase1 or PC-1	Interaction with the insulin receptor with consequent reduction of insulin receptor activity	rs1044498
IRS-1, insulin receptor substrate 1	Part of the machinery involved in insulin pathway as transductor of insulin receptor signaling	rs1801278
ADIPOQ, adiponectin	Relevant adipocytokine associated with insulin resistance, type 2 diabetes, and NAFLD pathogenesis	rs2241766 rs1501299
LEPR, leptin receptor	Receptor of leptin, a hormone synthesized by adipocytes that regulates food intake, insulin action, thermogenesis, and immune system	rs62589000
		rs6700986
		rs1137100
		rs1137101
		rs8179183
RETN, Resistin	Adipocytokine involved in lipid metabolism, hepatic insulin resistance, inflammatory cascade reactions, and fibrogenesis	rs3745367
PEMT, phosphatidylethanolamine N-methyltransferase	Enzyme involved in the de novo synthesis of phosphatidylcholine in the liver, a biochemical pathway essential for VLDL formation	rs7946
FATP5, Fatty Acid Transport Protein 5	Transporter involved in the hepatic uptake of fatty acids	rs56225452
ADRB2 and ADRB3, β-adrenergic receptor 2 and 3	β-adrenergic receptors, with several functions including regulation of basal metabolism and induction of lipolysis	rs4994
		rs1042714
		rs2053044
		rs11168070
		rs11959427
		rs1042711
PPARα, peroxisome proliferative activated receptor α	Transcription factor whose activation improves steatosis, inflammation, and fibrosis in pre-clinical models of NAFLD	rs1800206
PPARGC1A, peroxisome proliferator-activated receptor γ coactivator 1-α	PGC-1α, involved in mitochondrial functions, oxidative stress, gluconeogenesis, and lipogenesis	rs8192678
		rs2290602
PPARγ, peroxisome proliferative activated receptor γ	Transcription factor whose activation improves IR, restores adipose tissue insulin sensitivity, and decreases fatty free acids flux to the liver	rs1801282
APOE, apolipoprotein E	Mediator of remnant lipoprotein binding to LDL receptors to favor the clearance of chylomicrons and VLDL	N/A
APOC3, apolipoprotein C-III	A constituent of plasma VLDL, chylomicrons, and HDL-C that inhibits lipoprotein lipase and triglycerides clearance	rs2854116
		rs2854117
MTTP, microsomal triglyceride transfer protein	Transfer protein involved in apoB-lipoprotein assembly	rs1800591
		rs1800804
		rs1057613 rs3805335
LPIN1, lipin 1	Phosphatase specifically involved in metabolic pathways between adipose tissue and liver	rs13412852

SNP: Single nucleotide polymorphism; NAFLD: Nonalcoholic fatty liver disease; HDL-C: High-density lipoprotein-cholesterols; VLDL: Very low density lipoprotein; LDL: Low density lipoprotein.