Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target.
Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target.
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HSD17B13 基因变异是肝功能障碍的保护者吗？作为潜在治疗目标的未来前景。
DOI：
10.3390/jpm11070619
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发表时间：
2021-06-30
影响因子：
--
通讯作者：
Soto-Gutierrez A
中科院分区：
文献类型：
--
作者：
Motomura T;Amirneni S;Diaz-Aragon R;Faccioli LAP;Malizio MR;Coard MC;Kocas-Kilicarslan ZN;Frau C;Haep N;Ostrowska A;Florentino RM;Soto-Gutierrez A
随着饮食和生活方式的改变，脂肪肝(FLD)变得越来越普遍。许多遗传风险因素，如PNPLA3、TM6SF2、GCKR和MBOAT7的变异体，先前已通过全基因组关联研究(GWAS)发现与FLD相关。2018年，羟基类固醇17-β脱氢酶家族13(HSD17B13)的一个遗传变异(rs72613567，T>；TA)首次与小等位基因携带者发生酒精性肝病和非酒精性脂肪性肝病的风险降低有关。其他HSD17B13变异后来也分别与NAFLD患者较低的炎症评分或对NAFLD的保护有关(rs6834314，A>；G和rs9992651，G>；A)。HSD17B13是一种脂滴相关蛋白，但其功能尚不明确。与其他增加FLD风险的遗传变异相比，HSD17B13变异起到了保护作用，使该基因成为潜在的治疗靶点。然而，这些变异降低FLD发病风险的机制仍不清楚。由于对细胞系和小鼠模型的研究产生了相互矛盾的结果，使用诱导多能干细胞进行人类肝组织建模可能是向前迈进并解开这一谜团的最佳方式。
As diet and lifestyle have changed, fatty liver disease (FLD) has become more and more prevalent. Many genetic risk factors, such as variants of PNPLA3, TM6SF2, GCKR, and MBOAT7, have previously been uncovered via genome wide association studies (GWAS) to be associated with FLD. In 2018, a genetic variant (rs72613567, T > TA) of hydroxysteroid 17-β dehydrogenase family 13 (HSD17B13) was first associated with a lower risk of developing alcoholic liver disease and non-alcoholic fatty liver disease (NAFLD) in minor allele carriers. Other HSD17B13 variants were also later linked with either lower inflammation scores among NAFLD patients or protection against NAFLD (rs6834314, A > G and rs9992651, G > A) respectively. HSD17B13 is a lipid droplet-associated protein, but its function is still ambiguous. Compared to the other genetic variants that increase risk for FLD, HSD17B13 variants serve a protective role, making this gene a potential therapeutic target. However, the mechanism by which these variants reduce the risk of developing FLD is still unclear. Because studies in cell lines and mouse models have produced conflicting results, human liver tissue modeling using induced pluripotent stem cells may be the best way to move forward and solve this mystery.
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影响因子：
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作者：
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