Roberts A K, Monzon-Bordonaba F, Van Deerlin P G, Holder J, Macones G A, Morgan M A, Strauss J F, Parry S
Center for Research on Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, Philadelphia, USA.
Am J Obstet Gynecol. 1999 May;180(5):1297-302. doi: 10.1016/s0002-9378(99)70632-0.
The rarer allele of a polymorphism within the promoter region at position -308 of the gene for tumor necrosis factor alpha is associated with increased gene transcription. In this study we tested the hypothesis that this rarer allele is associated with spontaneous preterm birth.
We conducted a case-control study of women admitted to our labor and delivery unit. To assess data from a single racial group with a high incidence of preterm birth we restricted our analysis to African American women, who contributed 73.6% of the samples collected during the study period. Case patients (n = 55) were defined as women who were delivered before 37 weeks' gestation after idiopathic preterm labor or preterm premature rupture of membranes. Control subjects (n = 110) included women who were delivered after 37 weeks' gestation and had no history of preterm delivery. We also performed subgroup analyses of women with idiopathic preterm labor and delivery (n = 29) and women who were delivered preterm after preterm premature rupture of the fetal membranes (n = 26).
Although carriers (homozygotes plus heterozygotes) of the rarer allele of the polymorphism at position -308 in the gene for tumor necrosis factor alpha were not significantly more common among women who were delivered preterm (n = 24/55, 44%) than among control subjects (n = 33/110, 30%, P =.08, odds ratio 1.81, 95% confidence interval 0.92-3.54), carriers of the rarer allele were more common among women who were delivered preterm after preterm premature rupture of membranes (n = 15/26, 58%) than among control subjects (P =.008, odds ratio 3.18, 95% confidence interval 1.33-7.83).
Our results demonstrate an association between allelic variants of the polymorphism at position -308 in the gene for tumor necrosis factor alpha and preterm birth after preterm premature rupture of the fetal membranes. We hypothesize that host susceptibility to environmental factors, such as hyperresponsiveness of the gene for tumor necrosis factor alpha to genital tract infection, may promote preterm premature rupture of the fetal membranes and subsequent preterm delivery.
肿瘤坏死因子α基因启动子区域第 -308 位多态性的较罕见等位基因与基因转录增加有关。在本研究中，我们检验了这一较罕见等位基因与自发性早产相关的假设。
我们对入住我院分娩单元的女性进行了一项病例对照研究。为了评估来自早产发生率高的单一种族群体的数据，我们将分析限制在非裔美国女性中，她们在研究期间提供了 73.6% 的样本。病例患者（n = 55）定义为在特发性早产或胎膜早破后妊娠 37 周前分娩的女性。对照受试者（n = 110）包括妊娠 37 周后分娩且无早产史的女性。我们还对特发性早产分娩的女性（n = 29）和胎膜早破后早产的女性（n = 26）进行了亚组分析。
尽管肿瘤坏死因子α基因第 -308 位多态性较罕见等位基因的携带者（纯合子加杂合子）在早产女性（n = 24/55，44%）中并不比对照受试者（n = 33/110，30%）更常见（P = 0.08，比值比 1.81，95% 置信区间 0.92 - 3.54），但较罕见等位基因的携带者在胎膜早破后早产的女性（n = 15/26，58%）中比对照受试者更常见（P = 0.008，比值比 3.18，95% 置信区间 1.33 - 7.83）。
我们的结果表明，肿瘤坏死因子α基因第 -308 位多态性的等位基因变异与胎膜早破后早产之间存在关联。我们推测，宿主对环境因素的易感性，如肿瘤坏死因子α基因对生殖道感染的高反应性，可能促进胎膜早破及随后的早产。
