Racial disparity in maternal-fetal genetic epistasis in spontaneous preterm birth
Racial disparity in maternal-fetal genetic epistasis in spontaneous preterm birth
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DOI：
10.1016/j.ajog.2008.02.003
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发表时间：
2008-06-01
影响因子：
9.8
通讯作者：
Williams, Scott M.
中科院分区：
文献类型：
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作者：
Fortunato, Stephen J.;Menon, Ramkumar;Williams, Scott M.
目的：了解自发性早产中黑人和白色人肿瘤坏死因子-α、白细胞介素-6及其受体基因变异体之间遗传相互作用的差异。（n = 1195）从病例中收集（早产< 36周妊娠; n = 448），对照组（> 37周妊娠; n = 747），并对肿瘤坏死因子-α、肿瘤坏死因子受体1和肿瘤坏死因子受体2中的单核苷酸多态性进行基因分型，白细胞介素-6和白细胞介素-6受体基因座。多因素降维分析用于检验所有单位点和多位点组合预测妊娠结局的能力。在白色患者中，母体DNA中-7227位点单核苷酸多态性之间的多位点相互作用（白细胞介素-6），22，215（白细胞介素-6受体）和-3448（肿瘤坏死因子-α）对妊娠结局的预测率约为59.1%（P <0.02;比值比，2.3 [95%可信区间= 1.6-3.4]）。在白色胎儿DNA和黑色母体DNA中，没有观察到显著的相互作用模型。在黑人患者中，最好的上位模型是胎儿DNA中17，691处单核苷酸多态性之间的上位模型。（肿瘤坏死因子受体1）和-3448（肿瘤坏死因子-α），68.3%的时间预测妊娠结局（P <0.01;比值比，5.0 [95%置信区间= 2.6- 9.6]）。结论：多位点相互作用的分析发现/关联了黑人和白色患者母体和胎儿DNA的不同模型，早产作为结果。在两个种族中均未检测到显著的母胎相互作用。
OBJECTIVE: To understand the differences in genetic interactions among tumor necrosis factor-alpha, interleukin-6 and their receptor gene variants between black and white patients in spontaneous preterm birth.STUDY DESIGN: Maternal and fetal DNA (n = 1195) were collected from cases (preterm birth < 36 weeks' gestation; n = 448), controls (> 37 weeks' gestation; n = 747), and genotyped for single nucleotide polymorphisms in tumor necrosis factor-alpha, tumor necrosis factor receptor 1, and tumor necrosis factor receptor 2, interleukin-6, and interleukin-6 receptor loci. Multifactor dimensionality reduction analysis was used to test all single and multilocus combinations for the ability to predict pregnancy outcome.RESULTS: In white patients, multilocus interactions in maternal DNA between single nucleotide polymorphisms at -7227 (interleukin-6), 22,215 (interleuki-6 receptor) and -3448 (tumor necrosis factor-alpha) was predictive of approximately 59.1% (P < .02; odds ratio, 2.3 [95% confidence interval = 1.6-3.4]) of pregnancy outcome. In white fetal DNA and black maternal DNA, no significant interactive models were observed. In black patients, the best epistatic model was in fetal DNA between single nucleotide polymorphisms at 17,691 (tumor necrosis factor-receptor 1) and at -3448 (tumor necrosis factor-alpha) and was predictive of pregnancy outcome 68.3% of the time (P < .01; odds ratio, 5.0 [95% confidence interval = 2.6- 9.6]).CONCLUSION: Analyses of multilocus interactions found/associated different models in black and white patients in both maternal and fetal DNA with preterm birth as outcome. Significant maternal-fetal interactions were not detected in either race.