Vitamin D receptor gene polymorphism and bone mineral density in healthy Japanese women

Yamagata, Zentaro; Myamura, T; Iijima, Sumio; Asaka, Akio; Sasaki, M; Kato, Junzo; Koizumi, Kiyoshi

doi:10.1016/s0140-6736(94)91690-x

Cited by 138 publications

(66 citation statements)

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“…There is a variation in the distribution of VDR alleles among different racial groups. In oriental countries such as Japan the frequency of BB is low in the general population (16). In agreement with this fact, we did not detect any BB genotype in the 6 individuals of oriental extraction who participated in the present study.…”

Section: Discussionsupporting

confidence: 89%

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

Ramalho¹,

Lazaretti-Castro²,

Hauache³

et al. 1998

Braz J Med Biol Res

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Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 ± 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 ± 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 ± 6.6 years (mean ± SD). Analysis of VDR gene polymorphism by restriction fragment length polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5% BB, 42.5% Bb and 37% bb and did not differ significantly from the values obtained for group II (16% BB, 36% Bb and 48% bb) or for group III (10.2% BB, 47.6% Bb and 41.8% bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurrence of osteoporotic fractures with advancing age.

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Section: Discussionsupporting

confidence: 89%

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

Ramalho¹,

Lazaretti-Castro²,

Hauache³

et al. 1998

Braz J Med Biol Res

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“…In the original study ) and a wide range of further population studies across ethnic and racial groups, associations have been reported between VDR alleles and bone density. Several studies in Caucasian and Asian populations (Yamagata et al 1994;Fleet et al 1995;Koshiyama et al 1995;Riggs et al 1995;Gross et al 1996;Momson et al 1997;Tamai et al 1997) have shown an allelic effect between extreme homozygotes of perhaps 0.5 SD units, with a difference in bone density ranging from 4 to 13 %. Other studies have reported little or no effect in various Caucasian populations (Hustmyer et Barger-Lux et al 1995a, b;Garnero et al 1995;Keen et al 1995;Kroger et al 1995;Jorgensen et al 1996;Alahari et al 1997;Francis et al 1997;Gunnes et al 1997;McClure et al 1997;Vandevyver et al 1997).…”

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confidence: 99%

“…Given that bone mass is a critical determinant of fracture risk, it is important to recognize that bone density at any time in life depends on the total amount of bone formed by the early twenties and the subsequent loss with aging and after the menopause (Jones et al 1994a, b;Teegarden et al 1995;Young et al 1995). Put simply, fracture risk is highest in those who achieve low bone mass in early life and/or lose bone more rapidly with age and menopause.…”

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confidence: 99%

“…About that time the skeleton increases in size and length and total bone mass increases about three-fold during just a few years (Teegarden et al 1995;Young et al 1995). A key issue is the role of nutrition and physical activity in this development.…”

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confidence: 99%

“…Returning to the impact of nutritional factors, the initial studies in which VDR alleles were associated or linked with bone density were in populations with a moderate to low Ca intake (mean about 700 mg/d; Morrison et al , 1997Yamagata et al 1994;Tokita et al 1996;Tamai et al 1997). The studies showing the reverse VDR gene effect were associated with higher Ca intakes (means >lOOOmg/d; Houston et al 1996;Salamone et al 1996;Uitterlinden et al 1996) and in the 'no effect' studies, Ca intake lay between these extremes of Ca intake Hustmyer et Garnero et al 1995Garnero et al , 1996Jorgensen et al 1996;Alahari et al 1997;Francis et al 1997;Gunnes et al 1997).…”

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confidence: 99%

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Genetics, calcium intake and osteoporosis

Eisman

1998

Proc. Nutr. Soc.

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Osteoporosis is a major health problem worldwide, particularly with advancing age in both men and women. The strength of the skeleton in older age results from bone strength achieved in early adulthood and age-related and, in women, post-menopause-related bone loss. While trauma and the manner in which older people fall are important contributors to fracture risk, low bone mass is a major factor. Determinants of bone mass include external factors such as lifestyle, especially physical activity, and calcium intake. The wide variation in dietary calcium intake across countries does not correlate with osteoporotic fracture risk, presumably due to ethnic differences between and within populations. The twin approach has been useful in the identification of the major part of age-specific variation in bone density (and turnover), which is genetically determined. Exploring possible genetic factors, we reported that common allelic variations in the vitamin D receptor (VDR) gene were associated with indices of bone turnover and density. Subsequent studies, including our own, have found weaker effects. However, allelic effects of the VDR gene polymorphisms have now been reported in a wide range of, but not all, Caucasian and Asian populations in which they have been studied. In relation to possible physiological mechanisms, the VDR alleles correlate with differences in gut calcium absorption and response of bone density to long-term dietary calcium intake. Moreover, differences in response to active vitamin D compounds have been found in relation to VDR gene alleles. Understanding how these allelic variants, which are not associated with differences in

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