Association Study of Parathyroid Hormone Gene Polymorphism and Bone Mineral Density in Japanese Postmenopausal Women

Abstract

Association of BST B1 restriction fragment length polymorphism (RFLP) of the parathyroid hormone (PTH) gene with bone mineral density (BMD) was examined in 383 healthy postmenopausal women in Japan who were unrelated. The RFLP was represented as B or b, the capital letter signifying the presence of and the small letter the absence of restriction site for BST B1. The frequency of each genotype-BB, Bb, and bb-was 82.5%, 16.7%, and 0.8%, respectively. When we statistically compared age, years after menopause, body height, and body weight between the BB genotype and the Bb genotype groups, there was no significant difference between the groups. However, the lumbar BMD and the score of BMD adjusted for age and body weight (Z score) were significantly lower in the group of genotype Bb than in the BB: 0.859 +/- 0.019 g/cm2 versus 0.925 +/- 0. 011 (mean +/- SE, P = 0.01) and -0.412 +/- 0.138 versus 0.067 +/- 0. 082 (mean +/- SE, P = 0.01). In addition, the Z score of total body BMD in the Bb genotype group was lower than that in the BB group. Comparison of serum and urinary biochemical bone metabolic markers suggested that the subjects with Bb genotype might be in a relatively higher state of bone turnover than those with BB genotype. These results suggest that the polymorphism in the PTH gene would be a useful genetic marker for lower BMD and the susceptibility for osteoporosis.

LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density

“…Previous studies demonstrated that BMD is associated with several genes/proteins. They included genes for parathyroid hormone (PTH) (Hosoi et al 1999), alpha 1 chain of type I collagen (COL1A1) (Grant et al 1996), vitamin D receptor (VDR) (Morrison et al 1994), transforming growth factor beta 1 (TGFB1) (Yamada et al 1998;Bertoldo et al 2000), interleukin-6 (IL6) (Ota et al 2001), osteoprotegerin (OPG) (Ohmori et al 2002), and tumor necrosis factor receptor superfamily, member 1B (TNFRSF1B ) (Spotila et al 2000;Albagha et al 2002). However, conflicting results have been reported in some of them.…”

Association of a polymorphism of the dopamine receptor D4 gene with bone mineral density in Japanese men

“…Indeed, the p57 gene (chromosome 11p15.5), parathyroid hormone gene (11p15.3-15.1), and calcitonin gene (11p15.2-15.1), all of which have been associated with BMD (Hosoi et al 1999;Miyao et al 2000;Urano et al 2000), are located in close proximity to DRD4 (11p15.5). However, our present results suggest that DRD4 is a candidate locus for reduced bone mass in Japanese men.…”

Genetic and environmental factors affecting peak bone mass in premenopausal Japanese women

“…, VDR-5' 3) , estrogen receptor (ER) 4) , calcitonin receptor (CTR) 5) , parathyroid hormone (PTH) 6) , osteocalcin (OC) 7) , apolipoprotein E (ApoE) 8) , insulin-like growth factor 1 9) , transforming growth factor-β 1 10) , collagen type-I α1 11) , interleukin-6 12) , human leukocyte antigen 13) , and peroxisome proliferator-activated receptor γ 14) ; however, study results are controversial, and the importance of each genetic factor in the prevention of osteoporosis remains unknown.…”

“…Genotypes of the VDR (BsmI) 15) , VDR (FokI) 3) , ER (PvuII) 16) , CTR (AluI) 17) , PTH (BstBI) 6) , OC (HindIII) 7) , ApoE (HhaI) 18) , and FABP2 (HhaI) 19) were determined by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs), as previously described.…”