Identification and association analysis of single nucleotide polymorphisms in the human noggin (NOG) gene and osteoporosis phenotypes

Noggin, an extracellular bone morphogenic protein (BMP) antagonist, blocks BMP signaling and decreases osteoblastogenesis. The purpose of this study was to identify novel sequence variations in the human noggin gene and to perform association analyses of these variations with phenotypes related to osteoporosis. Novel single nucleotide polymorphisms (SNPs) were identified by resequencing 7 kb of the noggin gene region in 24 randomly selected Afro-Caribbean men without regard to their bone mineral density (BMD) level. We identified 22 SNPs in the 7 kb noggin gene region, only 2 of which were previously described in dbSNP (build 126). There were also 11 unvalidated SNPs from dbSNP that could not be verified in our sequence analysis. Ten of the 22 identified SNPs showed a minor allele frequency greater than 0.05. Seven of these common SNPs were genotyped in 2060 Afro-Caribbean men age 40 and older. None of the 7 SNPs were associated with BMD at the proximal femur or lumbar spine. Our analysis suggests that a common variation in the noggin gene is unlikely to have a major impact on BMD among older men of African ancestry.