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
Abstract Background To 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. Methods A...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Biology of Sex Differences |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13293-023-00553-4 |
| _version_ | 1797454076005318656 |
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| author | Honglei Duan Xu Wang Wenqian Qi Jingyi Shi Liang Han Guohua Wang Yanhui Xu Jia Liu Jiangbin Wang |
| author_facet | Honglei Duan Xu Wang Wenqian Qi Jingyi Shi Liang Han Guohua Wang Yanhui Xu Jia Liu Jiangbin Wang |
| author_sort | Honglei Duan |
| collection | DOAJ |
| description | Abstract Background To 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. Methods A 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. Results Two 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. Conclusions This 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. |
| first_indexed | 2024-03-09T15:32:00Z |
| format | Article |
| id | doaj.art-465c6872932d40caa2c152324a80484d |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-03-09T15:32:00Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-465c6872932d40caa2c152324a80484d2023-11-26T12:09:48ZengBMCBiology of Sex Differences2042-64102023-10-0114111410.1186/s13293-023-00553-4Two 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 infectionHonglei Duan0Xu Wang1Wenqian Qi2Jingyi Shi3Liang Han4Guohua Wang5Yanhui Xu6Jia Liu7Jiangbin Wang8Department of Gastroenterology, China-Japan Union Hospital of Jilin UniversityDepartment of Gastroenterology, China-Japan Union Hospital of Jilin UniversityDepartment of Gastroenterology, China-Japan Union Hospital of Jilin UniversityDepartment of Gastroenterology, China-Japan Union Hospital of Jilin UniversityDepartment of Pathology, China-Japan Union Hospital of Jilin UniversityDepartment of Gastroenterology and Nephrology, Songyuan Jilin Oilfield HospitalDepartment of Gastroenterology and Hepatology, People’s Hospital of Zhengzhou University and Henan Provincial People’s HospitalDepartment of Gastroenterology, China-Japan Union Hospital of Jilin UniversityDepartment of Gastroenterology, China-Japan Union Hospital of Jilin UniversityAbstract Background To 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. Methods A 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. Results Two 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. Conclusions This 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.https://doi.org/10.1186/s13293-023-00553-4Hepatitis B virusChronic HBV infectionSRD5A2Single nucleotide polymorphismSex hormoneSex hormone receptor |
| spellingShingle | Honglei Duan Xu Wang Wenqian Qi Jingyi Shi Liang Han Guohua Wang Yanhui Xu Jia Liu Jiangbin Wang 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 Hepatitis B virus Chronic HBV infection SRD5A2 Single nucleotide polymorphism Sex hormone Sex hormone receptor |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Hepatitis B virus Chronic HBV infection SRD5A2 Single nucleotide polymorphism Sex hormone Sex hormone receptor |
| url | https://doi.org/10.1186/s13293-023-00553-4 |
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