Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants.
Spontaneous preterm birth (<37 weeks gestation-PTB) occurs in approximately 12% of pregnancies in the United States, and is the largest contributor to neonatal morbidity and mortality. PTB is a complex disease, potentially induced by several etiologic factors from multiple pathophysiologic pathwa...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-09-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2553267?pdf=render |
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| author | Digna R Velez Stephen J Fortunato Poul Thorsen Salvatore J Lombardi Scott M Williams Ramkumar Menon |
| author_facet | Digna R Velez Stephen J Fortunato Poul Thorsen Salvatore J Lombardi Scott M Williams Ramkumar Menon |
| author_sort | Digna R Velez |
| collection | DOAJ |
| description | Spontaneous preterm birth (<37 weeks gestation-PTB) occurs in approximately 12% of pregnancies in the United States, and is the largest contributor to neonatal morbidity and mortality. PTB is a complex disease, potentially induced by several etiologic factors from multiple pathophysiologic pathways. To dissect the genetic risk factors of PTB a large-scale high-throughput candidate gene association study was performed examining 1536 SNP in 130 candidate genes from hypothesized PTB pathways. Maternal and fetal DNA from 370 US Caucasian birth-events (172 cases and 198 controls) was examined. Single locus, haplotype, and multi-locus association analyses were performed separately on maternal and fetal data. For maternal data the strongest associations were found in genes in the complement-coagulation pathway related to decidual hemorrhage in PTB. In this pathway 3 of 6 genes examined had SNPs significantly associated with PTB. These include factor V (FV) that was previously associated with PTB, factor VII (FVII), and tissue plasminogen activator (tPA). The single strongest effect was observed in tPA marker rs879293 with a significant allelic (p = 2.30x10(-3)) and genotypic association (p = 2.0x10(-6)) with PTB. The odds ratio (OR) for this SNP was 2.80 [CI 1.77-4.44] for a recessive model. Given that 6 of 8 markers in tPA were statistically significant, sliding window haplotype analyses were performed and revealed an associating 4 marker haplotype in tPA (p = 6.00x10(-3)). The single strongest effect in fetal DNA was observed in the inflammatory pathway at rs17121510 in the interleukin-10 receptor antagonist (IL-10RA) gene for allele (p = 0.01) and genotype (p = 3.34x10(-4)). The OR for the IL-10RA genotypic additive model was 1.92 [CI 1.15-3.19] (p = 2.00x10(-3)). Finally, exploratory multi-locus analyses in the complement and coagulation pathway were performed and revealed a potentially significant interaction between a marker in FV (rs2187952) and FVII (rs3211719) (p<0.001). These results support a role for genes in both the coagulation and inflammation pathways, and potentially different maternal and fetal genetic risks for PTB. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T15:44:26Z |
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| spelling | doaj.art-0101265128d348bb9ee784a1eff2db702022-12-21T18:58:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-09-0139e328310.1371/journal.pone.0003283Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants.Digna R VelezStephen J FortunatoPoul ThorsenSalvatore J LombardiScott M WilliamsRamkumar MenonSpontaneous preterm birth (<37 weeks gestation-PTB) occurs in approximately 12% of pregnancies in the United States, and is the largest contributor to neonatal morbidity and mortality. PTB is a complex disease, potentially induced by several etiologic factors from multiple pathophysiologic pathways. To dissect the genetic risk factors of PTB a large-scale high-throughput candidate gene association study was performed examining 1536 SNP in 130 candidate genes from hypothesized PTB pathways. Maternal and fetal DNA from 370 US Caucasian birth-events (172 cases and 198 controls) was examined. Single locus, haplotype, and multi-locus association analyses were performed separately on maternal and fetal data. For maternal data the strongest associations were found in genes in the complement-coagulation pathway related to decidual hemorrhage in PTB. In this pathway 3 of 6 genes examined had SNPs significantly associated with PTB. These include factor V (FV) that was previously associated with PTB, factor VII (FVII), and tissue plasminogen activator (tPA). The single strongest effect was observed in tPA marker rs879293 with a significant allelic (p = 2.30x10(-3)) and genotypic association (p = 2.0x10(-6)) with PTB. The odds ratio (OR) for this SNP was 2.80 [CI 1.77-4.44] for a recessive model. Given that 6 of 8 markers in tPA were statistically significant, sliding window haplotype analyses were performed and revealed an associating 4 marker haplotype in tPA (p = 6.00x10(-3)). The single strongest effect in fetal DNA was observed in the inflammatory pathway at rs17121510 in the interleukin-10 receptor antagonist (IL-10RA) gene for allele (p = 0.01) and genotype (p = 3.34x10(-4)). The OR for the IL-10RA genotypic additive model was 1.92 [CI 1.15-3.19] (p = 2.00x10(-3)). Finally, exploratory multi-locus analyses in the complement and coagulation pathway were performed and revealed a potentially significant interaction between a marker in FV (rs2187952) and FVII (rs3211719) (p<0.001). These results support a role for genes in both the coagulation and inflammation pathways, and potentially different maternal and fetal genetic risks for PTB.http://europepmc.org/articles/PMC2553267?pdf=render |
| spellingShingle | Digna R Velez Stephen J Fortunato Poul Thorsen Salvatore J Lombardi Scott M Williams Ramkumar Menon Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. PLoS ONE |
| title | Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. |
| title_full | Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. |
| title_fullStr | Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. |
| title_full_unstemmed | Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. |
| title_short | Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. |
| title_sort | preterm birth in caucasians is associated with coagulation and inflammation pathway gene variants |
| url | http://europepmc.org/articles/PMC2553267?pdf=render |
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