VITAMIN-D-RECEPTOR GENE START CODON POLYMORPHISMS (FOKI) AND BONE-MINERAL DENSITY - INTERACTION WITH AGE, DIETARY CALCIUM, AND 3'-END REGION POLYMORPHISMS

Osteoporosis is a polygenic disease, whose determining loci have not y et been identified. Vitamin D receptor (VDR) gene polymorphisms in the 3'-end region las determined by the enzymes BsmI and ApaI) have been inconsistently associated with bone mineral mass, More recently, VDR s tart codon polymorphisms las determined by the enzyme FokI) have been found to be related to adult bone mineral density (BMD) in pre-and pos tmenopausal American women. We investigated the association between BM D and FokI genotypes in premenopausal European-Caucasian women as well as in prepubertal girls from the same genetic background and examined the interaction with VDR S'-end region polymorphisms and,vith dietary calcium intake. Areal BMD (g/cm(2)) was measured by dual-energy X-ray absorptiometry at the level of the lumbar spine, femoral neck, and fe moral shaft in 177 healthy premenopausal women (age range, 18.7-56.0 y ears) as well as in 155 prepubertal girls (age range, 6.6-11.4 years). Genotyping for FokI, BsmI, and ApaI VDR polymorphisms was performed u sing polymerase chain reaction methods. FokI genotype-dietary calcium interaction was cross-sectionally analyzed in all subjects and longitu dinally in 103 prepubertal girls enrolled in a calcium intervention tr ial, The prevalence of FokI VDR gene polymorphisms in this cohort was 15% fore, 50% for Ff, and 35% for FF, In the whole cohort of premenopa usal women or prepubertal girls, no significant association was found between FokI VDR gene polymorphisms and BMD, even adjusted for age (Z score), weight, height, and calcium intake, Further analysis of FokI V DR gene polymorphisms and dietary calcium intake suggested a possible interaction in BMD determination, since a trend for an association wit h FokI genotypes was more evident at high than low calcium intake in b oth cross-sectional and longitudinal studies, Furthermore, cross-genot yping FokI and either BsmI or ApaI VDR polymorphisms suggested that th e ff genotype was associated with a significantly lower lumbar spine B MD in bb and nn prepubertal girls. FokI VDR gene polymorphisms were no t significantly associated with BMD in healthy European-Caucasian fema les. However, cross-genotyping of the VDR 3'-end and start codon polym orphic regions may provide a further insight into the complex determin ation of BMD.