A SNP implicated in preterm birth among African Americans

I thought this was a great paper because it investigated the phenomena from several angles:
- differences in genotype between many ancestry groups (including many Sierra Leone groups, for some reason)
- tissue culture and transfection
- EMSA
- population structure of study group
... and more


A functional SNP in the promoter of the SERPINH1 gene increases risk of 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 D. Shriver, Roberto Romero, and Jerome F. Strauss, III

PNAS Sept. 5, 2006; 103:13463-13467

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 <> 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 <> results. The combined case-control findings showed a highly significant (P <> 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.