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RSS FeedsSplice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease [Patient-Oriented and Epidemiological Research] (Journal of Lipid Research)

 
 

4 january 2019 14:01:23

 
Splice variant rs72613567 prevents worst histologic outcomes in patients with nonalcoholic fatty liver disease [Patient-Oriented and Epidemiological Research] (Journal of Lipid Research)
 




Hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) is a lipid droplet-associated protein; its gene-encoding variants affect the chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD). To estimate the effect of rs72613567, a splice variant with an adenine insertion (A-INS), on NAFLD susceptibility and severity, we performed a case-control study with 609 individuals. We investigated the effect of carrying the A-INS allele in 356 patients with biopsy-proven disease and explored the relationship between rs72613567 genotypes and the hepatic transcriptome. The A-INS allele protected against NAFLD [odds ratio (OR) per adenine allele = 0.667; 95% CI, 0.486–0.916; P = 0.012]; this effect was nonsignificant when logistic regression analysis included BMI. The A-INS allele protected against nonalcoholic steatohepatitis (NASH) (OR = 0.612; 95% CI, 0.388–0.964; P = 0.033), ballooning degeneration (OR = 0.474; 95% CI, 0.267–0.842; P = 0.01), lobular inflammation (OR = 0.475; 95% CI, 0.275–0.821; P = 0.007), and fibrosis (OR = 0.590; 95% CI, 0.361–0.965; P = 0.035). In patients carrying A-INS, HSD17B13 levels decreased proportionally to allele dosage. Whole-transcriptome genotype profiling showed overrepresented immune response-related pathways. Thus, the rs72613567 A-INS allele reduces the risk of NASH and progressive liver damage and may become a therapeutic target.


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38 viewsCategory: Cell Biology, Molecular Biology
 
Serum paraoxonase 1 activity is paradoxically maintained in nonalcoholic fatty liver disease despite low HDL cholesterol [Patient-Oriented and Epidemiological Research] (Journal of Lipid Research)
A comprehensive map of single-base polymorphisms in the hypervariable LPA kringle IV type 2 copy number variation region [Patient-Oriented and Epidemiological Research] (Journal of Lipid Research)
 
 
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