A functional SNP in the promoter of the SERPINH1 gene increases risk of preterm premature rupture of membranes in African Americans

Hongyan Wang, Samuel Parry, George Macones, Mary D. Sammel, Helena Kuivaniemi, Gerard Tromp, George Argyropoulos, Indrani Halder, Mark Shriver, Roberto Romero, Jerome F. Strauss

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Abstract

Prematurity is more prevalent in African Americans than in European Americans. We investigated the contribution of a functional SNP in the promoter of the SERPINH1 gene, enriched among those of African ancestry, to preterm premature rupture of membranes (PPROM), the leading identifiable cause of preterm birth. SERPINH1 encodes heat-shock protein 47, a chaperone essential for collagen synthesis. The SERPINH1 -656 minor T allele had a greater frequency in African populations and African Americans than in European Americans (12.4% vs. 4.1%). The -656 T allele displayed significantly reduced promoter activity compared to the major -656 C allele in amnion fibroblasts, which lay down the fibrillar collagen that gives tensile strength to the amnion. An initial case-control study demonstrated that the -656 T allele is significantly more frequent in African-American neonates (P < 0.0009) born from pregnancies complicated by PPROM compared with controls (odds ratio of 3.22, 95% confidence interval 1.50, 7.22). There was no significant difference in ancestry among cases and controls using a dihybrid model based on 29 ancestry-informative markers. Adjusting the results of the case-control study for admixture still yielded a statistically significant association between the -656 T allele and PPROM (P < 0.002). A follow-up case-control study gave similar results. The combined case-control findings showed a highly significant (P < 0.0000045) association between the -656 T allele and PPROM. The SERPINH1 -656 T allele is the first example of an ancestry-informative marker associated with preterm birth in African Americans.

Original languageEnglish (US)
Pages (from-to)13463-13467
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number36
DOIs
StatePublished - Sep 5 2006

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African Americans
Single Nucleotide Polymorphism
Alleles
Genes
Case-Control Studies
Amnion
Premature Birth
HSP47 Heat-Shock Proteins
Fibrillar Collagens
Tensile Strength
Preterm Premature Rupture of the Membranes
Collagen
Fibroblasts
Odds Ratio
Newborn Infant
Confidence Intervals
Pregnancy
Population

All Science Journal Classification (ASJC) codes

  • General

Cite this

Wang, Hongyan ; Parry, Samuel ; Macones, George ; Sammel, Mary D. ; Kuivaniemi, Helena ; Tromp, Gerard ; Argyropoulos, George ; Halder, Indrani ; Shriver, Mark ; Romero, Roberto ; Strauss, Jerome F. / A functional SNP in the promoter of the SERPINH1 gene increases risk of preterm premature rupture of membranes in African Americans. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 36. pp. 13463-13467.
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abstract = "Prematurity is more prevalent in African Americans than in European Americans. We investigated the contribution of a functional SNP in the promoter of the SERPINH1 gene, enriched among those of African ancestry, to preterm premature rupture of membranes (PPROM), the leading identifiable cause of preterm birth. SERPINH1 encodes heat-shock protein 47, a chaperone essential for collagen synthesis. The SERPINH1 -656 minor T allele had a greater frequency in African populations and African Americans than in European Americans (12.4{\%} vs. 4.1{\%}). The -656 T allele displayed significantly reduced promoter activity compared to the major -656 C allele in amnion fibroblasts, which lay down the fibrillar collagen that gives tensile strength to the amnion. An initial case-control study demonstrated that the -656 T allele is significantly more frequent in African-American neonates (P < 0.0009) born from pregnancies complicated by PPROM compared with controls (odds ratio of 3.22, 95{\%} confidence interval 1.50, 7.22). There was no significant difference in ancestry among cases and controls using a dihybrid model based on 29 ancestry-informative markers. Adjusting the results of the case-control study for admixture still yielded a statistically significant association between the -656 T allele and PPROM (P < 0.002). A follow-up case-control study gave similar results. The combined case-control findings showed a highly significant (P < 0.0000045) association between the -656 T allele and PPROM. The SERPINH1 -656 T allele is the first example of an ancestry-informative marker associated with preterm birth in African Americans.",
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A functional SNP in the promoter of the SERPINH1 gene increases risk of preterm premature rupture of membranes in African Americans. / Wang, Hongyan; Parry, Samuel; Macones, George; Sammel, Mary D.; Kuivaniemi, Helena; Tromp, Gerard; Argyropoulos, George; Halder, Indrani; Shriver, Mark; Romero, Roberto; Strauss, Jerome F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 36, 05.09.2006, p. 13463-13467.

Research output: Contribution to journalArticle

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T1 - A functional SNP in the promoter of the SERPINH1 gene increases risk of preterm premature rupture of membranes in African Americans

AU - Wang, Hongyan

AU - Parry, Samuel

AU - Macones, George

AU - Sammel, Mary D.

AU - Kuivaniemi, Helena

AU - Tromp, Gerard

AU - Argyropoulos, George

AU - Halder, Indrani

AU - Shriver, Mark

AU - Romero, Roberto

AU - Strauss, Jerome F.

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AB - Prematurity is more prevalent in African Americans than in European Americans. We investigated the contribution of a functional SNP in the promoter of the SERPINH1 gene, enriched among those of African ancestry, to preterm premature rupture of membranes (PPROM), the leading identifiable cause of preterm birth. SERPINH1 encodes heat-shock protein 47, a chaperone essential for collagen synthesis. The SERPINH1 -656 minor T allele had a greater frequency in African populations and African Americans than in European Americans (12.4% vs. 4.1%). The -656 T allele displayed significantly reduced promoter activity compared to the major -656 C allele in amnion fibroblasts, which lay down the fibrillar collagen that gives tensile strength to the amnion. An initial case-control study demonstrated that the -656 T allele is significantly more frequent in African-American neonates (P < 0.0009) born from pregnancies complicated by PPROM compared with controls (odds ratio of 3.22, 95% confidence interval 1.50, 7.22). There was no significant difference in ancestry among cases and controls using a dihybrid model based on 29 ancestry-informative markers. Adjusting the results of the case-control study for admixture still yielded a statistically significant association between the -656 T allele and PPROM (P < 0.002). A follow-up case-control study gave similar results. The combined case-control findings showed a highly significant (P < 0.0000045) association between the -656 T allele and PPROM. The SERPINH1 -656 T allele is the first example of an ancestry-informative marker associated with preterm birth in African Americans.

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