Abstract:

Objective: To investigate the relationship between rs12437118 polymorphisms in ESRRB-coding gene ESRRB and tuberculosis susceptibility in Han population in northern China. Methods: A total of 607 Han tuberculosis patients in northern China visited Beijing Chest Hospital affiliated to Capital Medical University from March 2018 to October 2019(the case group) and 660 Han staff of tuberculosis specialist hospitals in northern China (the health control group) were collected. Competitive allele-specific PCR (KASP) was used to determine the polymorphism of the ESRRB gene rs12437118 single nucleotide polymorphism (SNP). Serum levels of ESRRB protein were measured by enzyme-linked immunosorbent assay (ELISA). By comparing the differences between genotype and ESRRB protein, the relationship between ESRRB gene rs12437118 locus polymorphisms and tuberculosis susceptibility was analyzed. The association of ESRRB rs12437118 polymorphisms with tuberculosis was evaluated using different genetic models, including dominant and recessive models. Results: The frequencies of GG, GA and AA rs12437118 genotypes were 50.2% (305/607), 38.1% (231/607) and 11.7% (71/607) in the case group and 44.9% (296/660), 45.6% (301/660) and 9.5% (63/660) in the healthy control group, respectively, and the difference between the two groups was statistically significant (χ²=7.619, P=0.022). GA rs12437118 SNP genotype was significantly associated with a low risk of tuberculosis in the Han population in northern China (OR (95%CI)=1.34 (1.06-1.70), χ²=6.079, P=0.014). The serum ESRRB level in the case group (243.1 (174.3, 367.3) pg/μl) was significantly lower than that in the healthy control group (360.3 (240.0, 604.1) pg/μl)(Z=5.623, P<0.001). However, there were no significant difference in ESRRB levels with different rs12437118 genotypes between the case group and the control group. ESRRB levels of AA, GA and GG genotypes in the case group were 328.9 (226.3, 553.0) pg/μl, 232.6 (164.7, 379.7) pg/μl and 196.8 (150.1, 328.4) pg/μl, respectively (F=1.790, P=0.171); and in the control group were 427.5 (253.9, 619.4) pg/μl, 353.7 (247.8, 666.4) pg/μl and 303.3 (219.8, 519.1) pg/μl, respectively (F=1.751, P=0.177). Conclusion: There was a significant association between ESRRB rs12437118 GA genotype and tuberculosis susceptibility in Han population in northern China, and low expression of ESRRB in serum of tuberculosis patients was not associated with rs12437118 gene polymorphism.

Key words: Receptors, estrogen, Polymorphism, single nucleotide, Tuberculosis, Disease susceptibility