Genetic variation of HSD17B13 is associated with an increased risk of lean nonalcoholic fatty liver disease

Abstract Background/purpose: Carriage of HSD17B13 rs72613567:TA is associated with a reduced risk of nonalcoholic fatty liver disease (NAFLD); however, whether this protective effect exists in lean NAFLD remains unknown. Therefore, we compared the association of HSD17B13 rs72613567 and NAFLD between lean and non-lean individuals.Methods: We tested the association of HSD17B13 rs72613567 with NAFLD, cirrhosis, and hepatocellular carcinoma (HCC) in 313,309 individuals from the UK Biobank, including 1464 patients with NAFLD, 1559 with cirrhosis, and 526 with HCC. We calculated the minor allele frequency (MAF) of HSD17B13 rs72613567 and analyzed this SNP using codominant, dominant, and recessive models. Furthermore, we calculated the population-attributable fraction (PAF) and the combined PAF for five SNPs (HSD17B13 rs72613567, TM6SF2 rs58542926, MBOAT7 rs641738, PNPLA3 rs738409, and GCKR rs1260326) and used multifactor dimensionality reduction (MDR) to analyze the interactions between HSD17B13 and the other four SNPs. Results: The MAF of HSD17B13 rs72613567 was considerably higher in lean NAFLD (32.57%) than in non-lean NAFLD (26.16%). Moreover, homozygosity of the TA allele showed a significant risk effect in the codominant (OR = 1.94; 95% CI: 1.09–3.44) and recessive models (OR = 1.94; 95% CI: 1.12–3.35). By contrast, in the case of cirrhosis, HCC, and non-lean NAFLD, both homozygosity and heterozygosity of the TA allele showed a protective effect. Finally, the MDR analysis did not detect any interaction between HSD17B13 and the other four SNPs. Conclusion: The polymorphism of HSD17B13 rs72613567 is different between lean and non-lean NAFLD, and the TA allele showed a risk effect for lean NAFLD.