Noncoding RNAs in Nonalcoholic Fatty Liver Disease: Potential Diagnosis and Prognosis Biomarkers

Table 1

Candidate genes and variant associated with NAFLD: function and phenotype.

Pathway	Genes	Variant/SNP	Phenotype/function	Stage/phase	Studies	References
Lipid metabolism	PNPLA3	rs738409 C/G	Hepatic steatosis, histologic lobular inflammation, HCC fibrosis, lipolytic and lipogenic function in vitro	NAFLD/NASH/activated HSCs	GWAS, case-control	[22, 115],
	PPARγ	rs1801282 G/C	Protection against liver injury	NAFLD	Case-control, GWAS, meta-analysis	[116]
	LPIN1	rs13412852 C/T	Regulation of lipid metabolism, reduced lipolysis, decreased flux of FAs to the liver, decreased fibrosis	NAFLD	Case-control	[115]
	NCAN	rs2228603 C/T	Regulates cell adhesion and migration/hepatic steatosis	NAFLD	GWAS	[115]
	RETN	rs3745367 G/A	Involved in lipid metabolism, hepatic insulin resistance, inflammatory cascade reactions, and fibrogenesis	NAFLD	GWAS, case-control	[115]
Cholesterol biogenesis	SREBPF 1	rs11868035 A/G	The severity of steatosis and necroinflammation/impaired glucose homeostasis and lipoprotein and adiponectin responses to fat ingestion	NAFLD; NASH	Case-control	[117]
	SREBPF 2	rs2228314 G>C	Histological characteristics and NASH diagnosis	NASH	Case-control	[118]
Fatty acid uptake and transport	PPAR	rs1801282	Protection against liver injury	NAFLD	Case-control, GWAS, meta-analysis	[119]
	APOC3	rs2854116 T/C rs2854117 C/T	Hepatic steatosis/inhibits lipoprotein lipase and triglyceride clearance	NAFLD	Case-control, meta-analysis	[120]
	FABP1	rs2241883 T/C rs1545224G/A	Impact blood lipoprotein/lipid levels and responses to lipid-lowering therapy and glycogenolysis/fibrosis steatosis	NAFLD/NASH	Case-control	[121]
	MTTP	rs1800591; rs1800804; rs1057613	Synthesis and secretion of VLDL in the liver, transfer protein involved in apoB-lipoprotein assembly/hypobetalipoproteinemia; Fibrosis, steatosis, and increased histological grade of NASH	NAFLD/NASH	GWAS, case-control	[120]
Oxidative stress	PPARα	rs1800206	Steatosis, inflammation, and fibrosis; Activates fatty acid oxidation and hepatic lipid hydrolysis	NAFLD/NASH	GWAS, case-control	[121]
	PNPLA3	rs738409 C/G	Hepatic steatosis, histologic lobular inflammation, HCC development, fibrosis/lipolytic and lipogenic function in vitro	NAFLD/NASH/activated HSCs	GWAS, case-control	[120]
	TM6SF2	rs58542926	Hepatic steatosis, necroinflammation, ballooning, higher serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels/fibrosis, cirrhosis	NAFLD/NASH	GWAS	[22, 115],
	GCKR	rs780094 A>G rs1260326 C>T	Steatosis/fibrosis, inability to regulate glucose influx into hepatocytes, increased de novo lipogenesis	NAFLD/NASH	GWAS, meta-analysis	[20, 27],
	HSD17B13	rs72613567 T>A	Localizes to hepatocyte lipid droplets/decreased HSD17B13 and PNPLA3 production	↓NASH; ↓Fibrosis	Case-control	[20]
Insulin resistance	ADIPOQ	rs2241766 rs1501299	Insulin-sensitizing, anti-inflammatory adipokine/severity of liver disease and with an atherogenic postprandial lipoprotein profile in NASH	NAFLD	Case-control	[115]
	IRS1	rs1801278	Downstream regulator of insulin action, deceased insulin signaling/fibrosis	NAFLD	Case-control	[115]
	PPARγ C1α	rs8192678	Transcriptional coactivator that regulates genes involved in lipid and glucose metabolism	NAFLD	Case-control	[122]
	TCF7L2	rs7903146C/T	Regulates gene expression in cellular metabolism and growth	NAFLD	Case-control	[122]