Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D receptor density

Barger-Lux, M. Janet; Heaney, Robert P.; Hayes, James M.; DeLuca, Hector F.; Johnson, Mark; Gong, Gordon

doi:10.1007/bf00298438

Cited by 120 publications

(71 citation statements)

References 4 publications

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“…A 2% variation in bone mineral density could not explain the variation in body weight and BMI that we observed in our cohort, and, moreover, no differences in body weight or BMI were observed in most studies reporting VDR genotype-related differences in bone mineral density (17,30). A study of healthy, non-obese BMI , 30 kgam 2 Y premenopausal Caucasian women showed an association of bb genotypes with increased bone mineral density and with increased body weight (34). However, in that study, the association of the bb genotype with body weight was shown to be independent of variations in bone mineral density.…”

Section: Discussioncontrasting

confidence: 80%

Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset

Reis

Dubois‐Laforgue

et al. 2001

European Journal of Endocrinology

148

102

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Objective: Allelic variations in the vitamin D receptor (VDR) gene were reported to modulate insulin secretion in response to glucose. VDR was investigated as a candidate gene for type 2 diabetes mellitus (T2DM). Method: Four single nucleotide polymorphisms (SNPs) in intron 8 (BsmI, Tru9I, ApaI) and exon 9 (TaqI) of the VDR gene were examined in 309 unrelated French subjects with T2DM and 143 controls.Results: The distribution of alleles and genotypes of the four SNPs was similar in patients and controls. However, in patients whose age at diagnosis of diabetes was #45 years, homozygous subjects for the T-allele of the TaqI SNP had a higher body mass index (BMI) 31X7^6X7 kgam 2 Y P 0X0058 and an increased prevalence of obesity (81%, P 0X005 with respect to heterozygous subjects 27X95 X0 kgam 2 ; 46%) or homozygous subjects for the t-allele 27X7^5X0 kgam 2 ; 52%). Similar results were observed for homozygous subjects for the b-allele of the BsmI SNP. Logistic regression analysis demonstrated that TT homozygosity was independently associated with obesity in these subjects (odds ratio, 4.64; 95% con®dence interval (CI), 1.64±14.76; P 0X0056. Conclusion: VDR is not a major gene for T2DM in French Caucasians. However, polymorphisms in the VDR gene are associated with the susceptibility to obesity in subjects with early-onset T2DM. The pathophysiological mechanisms of these associations remain unexplained, but they could be related to a direct effect of vitamin D in adypocyte differentiation and metabolism, or to an indirect effect by modulation of insulin secretion.

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Section: Discussioncontrasting

confidence: 80%

Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset

Reis

Dubois‐Laforgue

et al. 2001

European Journal of Endocrinology

148

102

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“…These authors also comment on the low frequency of the BB genotype (n = 2) in the study of Kröger et al [45], which could greatly limit the conclusions of this work. In the group of healthy American women of the Barger-Lux et al [50]study, frequency of the BB genotype was similar to that of the bb , a frequency higher than that in other studies. As they found an association between the VDR genotype and body mass index (BMI), these authors suggested that the exclusion of patients with a BMI >30 kg/m 2 from the studies may be the reason for a lower proportion of the bb genotype.…”

Section: Vitamin D Receptor Genementioning

confidence: 88%

Genetic Determinants of Bone Mass

Audı́¹,

Garcia-Ramírez²,

Carrascosa³

1999

Horm Res Paediatr

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A genetic contribution to bone mass determination was first described in the early 70s. Elucidation of gene contribution to this has since been attempted through studies analyzing associations between bone mass acquisition and/or maintenance and polymorphic variations of several genes. The first to be described was the vitamin D receptor gene (VDR), initially claimed to contribute to almost 75% of the genetic variation in bone mineral density (BMD) in twin and general population studies. Not all of the studies published to date conclude that a clear relationship exists between polymorphic VDR alleles and BMD, and the molecular basis for the VDR gene polymorphisms influence on bone mineralization has not yet been clarified. Since then, other genes with a significant role in bone metabolism such as estradiol receptor, collagen type 1_α1, TGF-β₁, interleukin-6, calcitonin receptor, α₂-HS-glycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, β₃-adrenergic receptor, apolipoprotein E, PTH, IGF-I and glucocorticoid receptor have been analyzed. Some polymorphic variations in these genes have been associated in some works with significant differences in BMD, with even more significant contributions when associations of different gene polymorphisms were analyzed. Again, the molecular basis for the contribution of these alleles to bone mass determination has not yet been described. A different approach has been attempted by linkage analysis of loci involved in bone density in pedigrees with low BMD using BMD as a quantitative trait. Recent results do not confirm, in these families, any association with any of the previously reported genes, but rather with other as yet unidentified genes. The genetic contribution to mild variations in the general population, as a result of environmental and endogenous individual influences, probably differs completely from that providing a pathologic BMD.

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“…Studies by Ferrari et al (16) and Yamagata et al (36) support the finding of increased rates of bone loss in subjects with the BB genotype, but several other investigators failed to find any association between VDR alleles and rates of bone loss. (22)(23)(24) Barger-Lux et al (37) have reported that BMD, by minimizing the differences in bone size, may obscure the VDR gene effect on bone mass.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Polymorphisms, Bone Mineral Density, and Bone Metabolism in Postmenopausal Mexican–American Women

McClure

Eccleshall

Gross

et al. 1997

Journal of Bone and Mineral Research

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Common polymorphisms in the vitamin D receptor (VDR) gene have been shown to correlate with bone mineral density (BMD). However, attempts to replicate the original findings in other populations have yielded variable results. These disparities may reflect ethnic or environmental differences in the expression of the VDR effect upon BMD. We examined a relatively ethnically homogeneous group of 103 healthy postmenopausal Caucasian women of Mexican descent living in Northern California. We determined the VDR genotype and measured the BMD at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry, as well as several biochemical indices of mineral metabolism. The prevalence of the BB genotype, associated in previous studies with the lowest BMD, was 8% and highly linked to the tt genotype. Absolute and age-adjusted BMD at both hip and spine showed a trend toward lower BMD in the BB, AA, and tt genotypes, but this trend did not achieve statistical significance. There were no consistent intergroup differences in change in BMD over 2 years of follow-up, nor in mean serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, or total urinary pyridinolines. Intact parathyroid hormone concentrations were significantly higher in subjects with the AA genotype, with a trend toward higher values in those with the BB and tt genotypes as well. Our data suggest that there may be a decrease in BMD associated with the B, A, and t alleles, but the intergroup difference in BMD is 0.2-0.5 standard deviations (SD) at the lumbar spine and 0.3 SD at the femoral neck, decreases that are smaller than previously reported. Given the relatively low prevalence of the BB/tt genotype in Mexican-American Caucasians, a larger sample would be required to detect a significant association between VDR alleles and differences in BMD of the magnitude suggested by our data. We conclude that a genotype effect of this magnitude, if present, would be clinically relevant, but the impact on BMD is too small to detect with statistical significance in a study of this size. (J Bone Miner Res 1997;12:234-240)

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Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D receptor density

Cited by 120 publications

References 4 publications

Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset

Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset

Genetic Determinants of Bone Mass

Vitamin D Receptor Polymorphisms, Bone Mineral Density, and Bone Metabolism in Postmenopausal Mexican–American Women

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