The Methylation in B7-H4 and BTLA Genes are Associated with the Risk of Pulmonary Tuberculosis

Abstract

Background

The important roles of B7 homologous body 4 (B7-H4), B and T lymphocyte attenuator (BTLA) in patients with pulmonary tuberculosis (PTB) have been reported. This study aims to evaluate the association among B7-H4 and BTLA genes polymorphism, methylation and PTB susceptibility.

Methodology

Here, we assessed the possible relationship of 10 single nucleotide polymorphisms (SNPs) in B7-H4, BTLA genes with PTB susceptibility in a Chinese population (496 PTB patients and 502 controls) by SNPscan technique. Then, the B7-H4, BTLA genes methylation levels among 98 PTB patients and 97 controls were detected using MethylTarget technique.

Results

This study found no significant differences in allele and genotype frequencies of B7-H4 gene rs10754339, rs10801935, rs10923223, rs1937956, rs3738414, BTLA gene rs1982809, rs2971205, rs75368388, rs9288953 variants between PTB patients and controls. Haplotype analysis suggested that the lower frequencies of B7-H4 AATTG haplotype, BTLA GATT haplotype and the higher frequency of BTLA AGTC haplotype were found in PTB patients when compared with controls. We also found that the frequency of BTLA gene rs9288953 C allele was significantly increased in PTB patients with drug resistance. Moreover, the methylation levels of B7-H4 and BTLA genes in PTB patients were greater than that in controls, and rs10754339 variant in B7-H4 gene could affect its methylation level in PTB patients.

Conclusion

B7-H4, BTLA genes polymorphism might not affect PTB susceptibility, while the abnormal methylation levels of B7-H4, BTLA genes were associated with the genetic background of PTB.

Keywords:

• pulmonary tuberculosis
• single nucleotide polymorphisms
• DNA methylation
• B7-H4
• BTLA

Ethics Approval and Consent to Participate

This study was approved by the Ethical Committee of Anhui Chest Hospital (K2023-011). All the study subjects provided informed consent to participate in this study.

Data Sharing Statement

The data generated and analyzed by this study are available from the corresponding author on reasonable request.

Disclosure

Xue-Qian Cai and Qian Huang are co-first authors for this study. The authors report no conflicts of interest in this work.

Additional information

Funding

There is no funding to report.