Mineralization of the extracellular matrix of bone is an essential element of bone development, maintenance and repair. ALPL and ENPP1 genes and their products are known to be central in local regulation of bone mineralization. The present study investigates potential associations of ENPP1 and ALPL polymorphisms with several phenotypes reflecting bone size and hand BMD. The study sample included 310 Caucasian nuclear families. Forty SNPs in ALPL and 14 SNPs in ENPP1 genetic loci as well as pairwise haplotypes were tested for association with bone strength related traits. Our findings suggest that the region corresponding to exons 7 through 9 of the ALPL gene harbors functional polymorphism affecting both bone size at various skeletal sites (p-value ranged from 0.01 to 0.0001) and hand bone mineral density (p-value=0.0007). The other important finding of consistent association between bone size phenotypes and the 3' untranslated region of ENPP1 gene (p-value ranged from 0.01 to 0.001) imply functional significance of this region to bone growth. The considered anthropometric and radiographic bone phenotypes are closely related to bone fragility thus suggesting a role for both genes in osteoporosis. Further research is required to validate the relevancy of the potentially functional regions identified by our and other studies to normal and pathologic bone development as well as to determine the relevancy of the polymorphisms in ALPL and ENPP1 gene loci to clinical practice.
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