J Korean Soc Endocrinol.  2001 Feb;16(1):97-114.

Association Between Peak Bone Mass and Genetic Polymorphisms of the Vitamin D Receptor, Estrogen Receptor, and Type I Collagen 1 Genes in Healthy Young Korean Women

• Kim HK
• Kim SW
• Kim ES
• Kim GS

Abstract

BACKGROUND
Genetic suggest that strongest effect is observed in the premenopausal peak bone mass, which become less with age. However, the evaluation of candidate genes polymorphisms has been most frequently done in postmenopausal women and the results have been controversial. Therefore, we studied the possible association of the peak bone mass and candidate for osteoporosis genes polymorphism in premenopausal women.
METHODS
The associations between BMD and polymorphisms of the vitamin D receptor (3'-end region by BsmI restriction enzyme and start codon by FokI restriction enzyme), estrogen receptor (by PvuII and XbaI restriction enzyme), and type I collagen 1 (Sp1 binding site by MscI and BalI restriction enzyme) genes were examined in 100 healthy young Korean women who had a peak bone mass (age 20-35 years). Bone mineral densities were measured by dual energy X-ray absorptiometry (DEXA). Dietary calcium intake was also measured using a food frequency questionnaire.
RESULTS
The frequencies of the B allele of the vitamin D receptor gene BsmI polymorphism and the X allele in the estrogen receptor gene, XbaI polymorphisms were lower in Koreans than those in Caucasians. The allelic frequencies of the vitamin vitamin D receptor gene FokI polymorphism and the estrogen receptor gene PvuII polymorphism were similar to those of Caucasians. No significant association was found between BMD and the vitamin D receptor genotype according to BsmI or FokI polymorphisms. There was also no significant relation between the PvuII or XbaI polymorphisms of the estrogen receptor gene and BMD. The associations between BMD and cross-genotypes combining the vitamin D receptor gene (BsmI and FokI) and estrogen receptor gene (PvuII and XbaI) polymorphisms were also analyzed. Among the subjects who lacked the Bf haplotype of the vitamin D receptor gene, the BMD of the femoral neck area was significantly higher in subjects lacking Px haplotypes of the estrogen receptor gene than in those having Px haplotype (p < 0.05). When dietary calcium intake was taken into consideration, there were significant differences in BMD according to the cross-genotype in the group having a low calcium intake (< 500 mg/day). The subjects that lacked the Bf and Px haplotypes had a significantly higher BMD in the femoral neck (p < 0.01), Ward's triangle (p < 0.05), and in the trochanteric area (p < 0.05) than those who lacked Bf but a Px haplotype. We did not find a polymorphism in the Sp1 binding site of the type I collagen 1 gene in our subjects.
CONCLUSION
These data suggest that a complex interaction of vitamin D and the estrogen receptor gene with the dietary calcium intake, rather than a polymorphism of a single gene, may influence peak bone mass in healthy young Korean women.

MeSH Terms

Absorptiometry, Photon
Alleles
Binding Sites
Bone Density
Calcium
Calcium, Dietary
Codon, Initiator
Collagen Type I*
Estrogens
Female
Femur
Femur Neck
Genotype
Haplotypes
Humans
Osteoporosis
Polymorphism, Genetic*
Surveys and Questionnaires
Receptors, Calcitriol*
Vitamin D*
Vitamins*
Calcium
Calcium, Dietary
Codon, Initiator
Collagen Type I
Estrogens
Receptors, Calcitriol
Vitamin D
Vitamins