Abstract
BACKGROUND AND AIMS: In Europeans, variants in the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene impact liver histology in metabolic-associated fatty liver disease (MAFLD). The impact of these variants in ethnic Chinese is unknown. The aim of this study was to investigate the potential associations in Chinese patients. METHODS: In total, 427 Han Chinese with biopsy-confirmed MAFLD were enrolled. Two single nucleotide polymorphisms in HSD17B13 were genotyped: rs72613567 and rs6531975. Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology. RESULTS: In our cohort, the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis [odds ratio (OR): 2.93 (1.20-7.17), p=0.019 for the additive model; OR: 3.32 (1.39-7.91), p=0.007 for the recessive model], representing an inverse association as compared to the results from European cohorts. In contrast, we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant [OR: 0.48 (0.24-0.98), p=0.043 for the additive model; OR: 0.62 (0.40-0.94), p=0.025 for the dominant model]. HSD17B13 variants were only associated with fibrosis but no other histological features. Furthermore, HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis. CONCLUSIONS: HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans. These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.