Tumor necrosis factor-alpha gene G308A polymorphism is associated with the risk of preterm delivery.

Objective: To investigate the association between polymorphism in tumor necrosis factor-alpha(TNF-alpha)/G308A and preterm delivery (PTD). Between July 1999 and June 2001, we conducted a molecular epidemiological study on genetic determinants of PTD at Anqing Hospital, China.

Methods: In a case-control-parent triads study, we investigated a total of 133 nuclear families: 79 normal gestational age families and 54 PTD families. A DNA extraction and polymerase chain reaction followed by restriction fragment length polymorphism analysis were used to genotype for the presence of TNF-alpha/G308A polymorphism.

Results: Gestational age was analyzed as a binary variable. Multiple logistic regression analysis results showed that TNF-alpha/A308A genotype was significantly increased the risk of preterm delivery (OR = 0.039, 95% CI: 1.14-128.75). In consistence with the population based multiple logistic regression analysis, Family Based Association Test (FBAT) analysis showed that TNF-alpha/308A allele was associated with preterm delivery as 308A-recessive inheritance model and 308A-additive inheritance model both gave rise to the significant result (P = 0.040 and P = 0.018 respectively).

Conclusion: Carriage of the mutant 308A allele of TNF-alpha/G308A polymorphism is associated with preterm delivery, which may be genuine etiologic factors of PTD.