Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target

Area of Science:

• Genetics
• Hepatology
• Molecular Biology

Background:

• Fatty liver disease (FLD), including non-alcoholic fatty liver disease (NAFLD), is increasingly prevalent due to changing diet and lifestyle.
• Genome-wide association studies (GWAS) have identified genetic risk factors like PNPLA3, TM6SF2, GCKR, and MBOAT7.
• Genetic variants in the hydroxysteroid 17-β dehydrogenase family 13 (HSD17B13) gene have been linked to a reduced risk of FLD and NAFLD.

Purpose of the Study:

• To investigate the protective role of HSD17B13 variants against fatty liver disease.
• To understand the ambiguous function of HSD17B13, a lipid droplet-associated protein.
• To explore the unclear mechanism by which HSD17B13 variants confer protection against FLD.

Main Methods:

• Review of existing genetic association studies (GWAS).
• Analysis of HSD17B13 variants (e.g., rs72613567, rs6834314, rs9992651) and their association with FLD/NAFLD.
• Consideration of cell line and mouse models, noting conflicting results.

Main Results:

• HSD17B13 variants (rs72613567, rs6834314, rs9992651) are associated with a lower risk of developing FLD and NAFLD.
• These variants may reduce inflammation in NAFLD patients.
• HSD17B13 variants present a protective role, contrasting with other known FLD risk variants.

Conclusions:

• HSD17B13 variants represent a potential therapeutic target for fatty liver disease due to their protective effect.
• The precise mechanism underlying HSD17B13's protective role remains elusive.
• Human liver tissue modeling using induced pluripotent stem cells is proposed as a promising approach to elucidate the mechanism.