Exploration of Medicine

Table 1

List of the main genetic variants associated with the histological spectrum of MAFLD

Variant	Gene	Function	Effect	Impact	Phenotype
rs738409 C > G	PNPLA3	Lipid remodeling	p.I148M	Loss-of-function	↑ MAFLD, NASH, fibrosis, HCC
rs58542926 C > T	TM6SF2	VLDL secretion	p.E167K	Loss-of-function	↑ MAFLD, NASH, fibrosis
rs641738 C > T	TMC4/MBOAT7	Lipid remodeling	p.G17E	Loss-of-function	↑ MAFLD, NASH, fibrosis, HCC
rs1260326 C > T	GCKR	Regulation of de novo lipogenesis	p.P446L	Loss-of-function	↑ MAFLD, NASH, fibrosis
rs72613567 T > TA	HSD17B13	Lipid remodeling	Truncated protein	Loss-of-function	↓ NASH, fibrosis, HCC
rs4841132 G > A	PPP1R3B	Glycogen synthesis	Non-coding	Gain-of-function	↓ MAFLD, fibrosis, HCC
rs1801278 A > C	IRS1	Insulin signaling	p.G972R	Loss-of-function	↑ Fibrosis
rs1044498 A > C	ENPP1	Insulin signaling	p.K121Q	Gain-of-function	↑ Fibrosis
rs2954021 G > A	TRIB1	Regulation of de novo lipogenesis	Non-coding	Gain-of-function	↑ MAFLD
rs12137855 C > T	LYPLAL1	Lipid metabolism	Intronic	Loss-of-function	↑ MAFLD
Several	APOB	VLDL secretion	Protein change	Loss-of-function	↑ MAFLD, NASH, fibrosis, HCC
Several	MTTP	VLDL secretion	Protein change	Loss-of-function	↑ MAFLD
rs236918 G > C	PCSK7	Membrane transferrin receptor shedding and regulation of circulating lipids	Intronic	Gain-of-function	↑ NASH, fibrosis
Several	PCSK9	LDL uptake	Protein change	Loss-of-function	No evidence of association with steatosis
Several	LIPA	Lipid remodeling	Protein change	LAL deficiency	↑ MAFLD, NASH, fibrosis
rs56225452 G > A	FATP5	FFAs uptake	Non-coding	Gain-of-function	↑ NASH, fibrosis
rs13412852 C > T	LPIN1	Lipid metabolism	Intronic	NA	↓ NASH, fibrosis
rs17618244 G > A	KLB	FGF19/FGFR4 pathway	R728Q	Loss-of-function	↓ NASH, fibrosis
rs4374383 G > A	MERTK	Innate immunity	Intronic	Loss-of-function	↓ Fibrosis
rs3750861 G > A	KLF6	HSCs activation	Splice variant IVS1-27G	Loss-of-function	↓ Fibrosis
Several	TERT	Telomere maintenance	Protein change	Loss-of-function	↑ Fibrosis, HCC
rs12979860 C > T	IL28B	Innate immunity	Alternative IFNL3/4 transcription	Loss-of-function	↓ NASH, Fibrosis
rs3480 A > G	FNDC5	HSCs activation	Non-coding	Loss-of-function	↓ Fibrosis
rs4880 C > T	SOD2	Mitochondrial antioxidant	p.A16V	Loss-of-function	↑ Fibrosis
rs695366 G > A	UCP2	Mitochondrial lipid metabolism Oxphos	-866 promoter variant	Gain-of-function	↓ NASH, fibrosis
rs2642438 G > A	MARC1	Mitochondrial detoxification	A165T	Loss-of-function	↓ MAFLD, NASH, fibrosis

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NA: not applicable