Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection

Biology of Sex Differences

Research

Yanhui Xu¹  Guohua Wang²  Jingyi Shi³  Jiangbin Wang³  Wenqian Qi³  Jia Liu³  Xu Wang³  Honglei Duan³  Liang Han⁴ 

[1] Department of Gastroenterology and Hepatology, People’s Hospital of Zhengzhou University and Henan Provincial People’s Hospital, 450003, Zhengzhou, Henan, China;Department of Gastroenterology and Nephrology, Songyuan Jilin Oilfield Hospital, 138000, Songyuan, Jilin, China;Department of Gastroenterology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai St., 130033, Changchun, Jilin, China;Department of Pathology, China-Japan Union Hospital of Jilin University, 130033, Changchun, Jilin, China;

关键词: Hepatitis B virus;    Chronic HBV infection;    SRD5A2;    Single nucleotide polymorphism;    Sex hormone;    Sex hormone receptor;    Sex difference;   

DOI  :  10.1186/s13293-023-00553-4

 received in 2023-07-27, accepted in 2023-09-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTo examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection.MethodsA total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients.ResultsTwo SNP loci in the SRD5A2 gene (rs12470143 and rs7594951) exhibited significant differences in genotype and allele frequencies between sexes, with the proportion of T alleles significantly higher in males than in females. It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype. Additionally, serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients. Female patients exhibited significantly lower serum DNA levels compared to male patients. Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores. Furthermore, multivariate analysis showed that the two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T), together with the male sex, age > 50 years old, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis.ConclusionsThis study demonstrated that two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T) are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.

【 授权许可】

CC BY   
© Society for Women's Health Research and BioMed Central Ltd. 2023

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