The −839(A/C) Polymorphism in the ECE1 Isoform b Promoter Associates With Osteoporosis and Fractures

CONTEXT: We previously found that variation in a quantitative trait locus, including the gene-encoding endothelin-converting enzyme 1 (Ece1), accounted for 40% of the variance in bone biomechanics and bone mineral density (BMD) in an intercross of recombinant congenic mouse strains. OBJECTIVE: We hypothesized that single nucleotide polymorphisms (SNPs) within the human ECE1 isoform b promoters, at ECE1 b −338(G/T) and ECE1 b −839(A/C), would associate with osteoporosis in postmenopausal women. DESIGN: We genotyped DNA for the ECE1 −338(G/T) and −839(A/C) SNPs. SETTING: A community medical center. PARTICIPANTS: Postmenopausal women (3564) with ≥1 dual-energy X-ray absorptiometry scan ≥60 years of age. MAIN OUTCOME MEASURES: BMD, osteoporosis, and clinical fractures. RESULTS: In multivariate models controlling for age, weight, healthcare duration, and tobacco, the CC genotype reduced the odds of lifetime fracture (OR 0.33, 95% CI 0.12, 0.87) and fracture ≥50 years of age (OR 0.31, 95% CI 0.11, 0.87), whereas the AC genotype increased odds of osteoporosis (OR 1.34, 95% CI 1.02 1.78) relative to the AA genotype. However, when controlling the false-discovery rate, findings were no longer significant. We found no consistent relationship between the ECE1 b −338(G/T) and study outcomes. CONCLUSIONS: The CC genotype was associated with fewer fractures, whereas the AC genotype was associated with osteoporosis. Our small sample size and few minorities are study limitations. Findings should be tested in another cohort to confirm a link between the ECE1 −839(A/C) SNPs and osteoporosis.