Roles of TNF-alpha gene polymorphisms in the occurrence and progress of SARS-Cov infection: a case-control study.
BACKGROUND
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)-alpha gene polymorphisms with the occurrence of SARS-CoV infection and its role in prognosis of patients with lung interstitial fibrosis and femoral head osteonecrosis.


METHODS
The association between genetic polymorphisms of TNF-alpha 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-alpha 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-alpha gene in locus of the promoter region and univariate logistic analysis was conducted in analyzing the collected data.


RESULTS
Compared 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-alpha 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.


CONCLUSIONS
SNPs of TNF-alpha 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.
Wang
Shixin
S
Department of Epidemiology, Medical College of Chinese People's Armed Police Force, Tianjin, China. Wshx-001@163.com
Wei
Maoti
M
Han
Yi
Y
Zhang
Keju
K
He
Li
L
Yang
Zhen
Z
Su
Bing
B
Zhang
Zhilun
Z
Hu
Yilan
Y
Hui
Wuli
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D005271:Femur Head Necrosis / Q000150:complications / Q000235:genetics*; D005838:Genotype; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000150:complications / Q000235:genetics*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000472:pathogenicity; D045169:Severe Acute Respiratory Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha