Chen Dafang, Hu Yonghua, Wu Baiyan, Chen Li, Fang Zhi'an, Yang Fan, Wang Lihua
Department of Cell Biology and Genetics, Peking University School of Basic Medical Sciences, Beijing, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2003 Aug;35(4):377-81.
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.
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.
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).
Carriage of the mutant 308A allele of TNF-alpha/G308A polymorphism is associated with preterm delivery, which may be genuine etiologic factors of PTD.
研究肿瘤坏死因子-α(TNF-α)基因G308A多态性与早产(PTD)之间的关联。1999年7月至2001年6月,我们在中国安庆医院开展了一项关于早产遗传决定因素的分子流行病学研究。
在一项病例对照亲代三联体研究中,我们共调查了133个核心家庭:79个正常孕周家庭和54个早产家庭。采用DNA提取、聚合酶链反应及限制性片段长度多态性分析对TNF-α/G308A多态性进行基因分型。
将孕周作为二元变量进行分析。多因素logistic回归分析结果显示,TNF-α/A308A基因型显著增加早产风险(OR = 0.039,95%CI:1.14 - 128.75)。与基于人群的多因素logistic回归分析结果一致,基于家系的关联检验(FBAT)分析显示,TNF-α/308A等位基因与早产相关,因为308A隐性遗传模型和308A加性遗传模型均得出显著结果(分别为P = 0.040和P = 0.018)。
TNF-α/G308A多态性的突变308A等位基因携带者与早产相关,这可能是早产的真正病因。