Rare coding variants in ALPL are associated with low serum alkaline phosphatase and low bone mineral density.

ABSTRACT: Alkaline phosphatase (ALP) plays an essential role in the regulation of tissue mineralization, and its activity is highly heritable. Guided by genetic associations discovered in a murine model, we hypothesized a role for rare coding variants in determining serum ALP level and bone mineral density (BMD) in humans. We sequenced the coding regions of the ALP gene (ALPL) in men with low and normal serum ALP activity levels. Single-nucleotide ALPL variants, including 19 rare nonsynonymous variants (minor allele frequency <1%), were much more frequent among the low ALP group (33.8%) than the normal group (1.4%, p = 1 × 10(-11)). Within the low ALP group, men with a rare, nonsynonymous variant had 11.2% lower mean serum ALP (p = 3.9 × 10(-4)), 6.7% lower BMD (p = 0.03), and 11.1% higher serum pho

SUBMITTER: Nielson CM 

PROVIDER: S-EPMC3810303 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature