From the Department of Obstetrics and Gynecology and the Center for Human Genomics at Wake Forest University Health Sciences, Winston-Salem, North Carolina; the Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Wayne State University, Detroit, Michigan; the University of Utah Health Sciences Center, Salt Lake City, Utah; The Ohio State University, Columbus, Ohio; Northwestern University, Chicago, Illinois; Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio; the University of Alabama at Birmingham, Birmingham, Alabama; the University of Texas Health Science Center at Houston, Houston, Texas; the University of Texas Medical Branch, Galveston, Texas; The George Washington University Biostatistics Center, Washington DC; the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Obstet Gynecol. 2011 Jan;117(1):125-130. doi: 10.1097/AOG.0b013e318202b2ef.
To estimate whether there is an association between length of gestation and gene polymorphisms that effect transcription of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), or interleukin-1β (IL-1β).
Blood for DNA analysis was collected from 834 women at high risk enrolled in a randomized, clinical trial of omega-3 fatty acid supplementation for the prevention of recurrent preterm birth. Genotyping was performed for three single nucleotide polymorphisms (SNPs), TNF-α -308, IL-6 -174, and IL-1β +3954. Women with the homozygous minor genotype were compared with women with either the heterozygous or the homozygous major genotype. Kaplan-Meier curves of gestational age at delivery and odds ratios for extreme preterm delivery were adjusted for African-American race and treatment group.
Women who were homozygous for the minor allele at the -308 position in the promoter region of the TNF-α gene had significantly shorter length of gestation than women who were either heterozygous or homozygous for the major allele (adjusted hazard ratio 1.74, 95% confidence interval [CI] 1.04-2.90, P=.03). Among women with this genotype, 20% (3/15) experienced extreme spontaneous preterm delivery (less than 28 weeks of gestation; adjusted odds ratio 7.51, 95% CI 1.84-30.72, P=.005). There was no difference in length of gestation or risk of extreme spontaneous preterm delivery by genotype for the IL-6 -174 or the IL-1β +3954 SNP.
Polymorphism at the -308 position in the TNF-α promoter region is associated with shorter gestation and an increased risk of spontaneous extreme preterm delivery.
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902.
II.
评估妊娠期长短与影响肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）或白细胞介素-1β（IL-1β）转录的基因多态性之间是否存在关联。
从参加ω-3 脂肪酸补充剂预防复发性早产的随机临床试验的 834 名高危孕妇中采集血液进行 DNA 分析。对 TNF-α-308、IL-6-174 和 IL-1β+3954 三个单核苷酸多态性（SNP）进行基因分型。将同型纯合子的女性与杂合子或同型纯合子的女性进行比较。对分娩时的胎龄进行 Kaplan-Meier 曲线分析，并调整非裔美国人种族和治疗组对早产的极端风险比。
TNF-α 基因启动子区-308 位置的纯合子女性的妊娠期明显短于杂合子或纯合子女性（调整后的危险比 1.74，95%置信区间 [CI] 1.04-2.90，P=0.03）。在这种基因型的女性中，有 20%（3/15）经历了极端自发性早产（妊娠不足 28 周；调整后的比值比 7.51，95%置信区间 1.84-30.72，P=0.005）。IL-6-174 或 IL-1β+3954 SNP 的基因型与妊娠期长短或自发性早产的极端风险之间没有差异。
TNF-α 启动子区-308 位置的多态性与妊娠时间缩短和自发性早产的极端风险增加有关。
ClinicalTrials.gov，www.clinicaltrials.gov，NCT00135902。
II 级。
