Abstract

BackgroundHost genetic factors may play a role in the occurrence and progress of SARS-Cov infection. This study was to investigate the relationship between tumor necrosis factor (TNF)-α gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis.MethodsThe association between genetic polymorphisms of TNF-α gene and susceptibility to severe acute respiratory syndromes (SARS) was conducted in a hospital-based case-control study including 75 SARS patients, 41 health care workers and 92 healthy controls. Relationships of TNF-α gene polymorphisms with interstitial lung fibrosis and femoral head osteonecrosis were carried out in two case-case studies in discharged SARS patients. PCR sequencing based typing (PCR-SBT) method was used to determine the polymorphisms of TNF-α gene in locus of the promoter region and univariate logistic analysis was conducted in analyzing the collected data.ResultsCompared to TT genotype, the CT genotype at the -204 locus was found associated with a protective effect on SARS with OR(95%CI) of 0.95(0.90–0.99). Also, TT genotype, CT and CC were found associated with a risk effect on femoral head necrosis with ORs(95%CI) of 5.33(1.39–20.45) and 5.67(2.74–11.71), respectively and the glucocorticoid adjusted OR of CT was 5.25(95%CI 1.18–23.46) and the combined (CT and CC) genotype OR was 6.0 (95%CI 1.60–22.55) at -1031 site of TNF-α gene. At the same time, the -863 AC genotype was manifested as another risk effect associated with femoral head necrosis with OR(95%CI) of 6.42(1.53–26.88) and the adjusted OR was 8.40(95%CI 1.76–40.02) in cured SARS patients compared to CC genotype.ConclusionSNPs of TNF-α gene of promoter region may not associate with SARS-CoV infection. And these SNPs may not affect interstitial lung fibrosis in cured SARS patients. However, the -1031CT/CC and -863 AC genotypes may be risk factors of femoral head necrosis in discharged SARS patients.

Highlights

  • Host genetic factors may play a role in the occurrence and progress of severe acute respiratory syndromes (SARS)-Cov infection

  • In order to explore more host factors influencing the occurrence of SARS-CoV infection, we studied the polymorphisms of tumor necrosis factor (TNF)-α gene at the promoter region, which had been ascribed to polymorphisms within the regulatory regions or signal sequences of cytokine genes [14]

  • We aimed to study whether polymorphisms in TNF-α promoter region were associated with SARS-CoV infection, development, and progression of interstitial lung fibrosis and femoral head necrosis in cure SARS patients

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Summary

Introduction

Host genetic factors may play a role in the occurrence and progress of SARS-Cov infection. This study was to investigate the relationship between tumor necrosis factor (TNF)-α gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis. TNF, the gene encoding tumour necrosis factor (TNF), resides in the central part (class III region) of the major histocompatibility complex (MHC) surrounded by a large number of other immunological genes [1]. The dual role of TNF, acting as an agent of both innate immunity and inflammatory pathology, poses a considerable challenge for gene regulation [2], and this regulation mainly located on promoter region of this gene. A number of studies had shown that the TNF-α promoter polymorphism had a significant effect on its transcriptional activity [6,7]

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