Huibert A P Pols

..For men, no clear association was found, possibly due to insufficient power. No clear association between testosterone and incident vertebral fractures was observed in either men or women...

..Interaction of ESR2 with ESR1 and IGF1 was determined and revealed a deleterious genetic combination that enhances the risk of osteoporotic fracture...

..An example is catechol-O-methyltransferase (COMT), an estrogen-degrading enzyme involved in inactivation of catechol-estrogens. Its gene contains a functional valine to methionine substitution at codon 158...

..5 cm shorter per allele copy of the ESR1 haplotype 1 (P for trend = 0.03). In conclusion, we demonstrate a role for genetic variations in the estrogen receptor alpha gene in determining adult stature in women...

..5; 95% CI, 1.1-2.0) of fragility fracture in women (n = 4212) but not in men (n = 2799). An approximation of hip bone geometry (from DXA) suggested the polymorphism is associated with bone strength and stability in gender-specific ways...

..Since age at menopause has a strong genetic component, we investigated the role of AMH signaling using a candidate gene approach...

..In conclusion, although functional changes of the LHR 291Ser candidate allele were observed, no associations with breast cancer were found, while the LHR 312Asn allele can be regarded as a weak breast cancer risk allele...

..05). All associations were independent of age and gender. Our study demonstrated that the genetic effect of the DBP gene on fracture risk appears only in combination with other genetic and environmental risk factors for bone metabolism...

..We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis...

..Their beneficial effects are thought to be mediated by GC transrepression on gene expression. However, their use is limited by serious adverse effects, presumably mediated by GC transactivation of gene expression...

..Inverse associations after adjustment for BMI suggest that android fat deposition as measured by the WHR, WTR, and DXA-based android-to-gynoid fat ratio is not beneficial and possibly even deleterious for bone...

..Due to a replacement of part of the CYP3A7 promoter with a sequence identical with the same region in the CYP3A4 promoter (referred to as CYP3A7*1C), some individuals still express a variant of the CYP3A7 gene later in life...

..02). The molecular mechanism whereby these moderate SOST genotype effects are mediated remains to be elucidated, but it is likely to involve differences in regulation of SOST gene expression...

..SIRT1 has pleiotropic metabolic functions. We investigated whether SIRT1 genetic variation is associated with obesity...

..Correction of niacin deficiency and SIRT1 modulators may prolong the life span of patients with diabetes...

..This study was undertaken to investigate whether genetic variations in the estrogen receptor alpha (ESR1) gene are associated with incident AMD...

..CRP levels were associated with pulse wave velocity (p = 0.007). In conclusion, the interleukin-6-174 G/C polymorphism is associated with increased arterial stiffness and pulse pressure...

..LRP5 variation was associated to both BMD and frame size, whereas both LRP5 and 6 variations were associated with an increased fracture risk in males...

..It has been suggested that the estrogen receptor alpha (ESR1) gene may influence peripheral E(2) levels, but the role of common sequence variations in the ESR1 gene is unclear...

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..We recently identified promoter and 3'-untranslated region (UTR) haplotype alleles that influence vitamin D receptor (VDR) mRNA expression...

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..04) in the risk of retinopathy was observed compared with participants with the wild-type genotype. In conclusion, our findings suggest that this IGF-I gene polymorphism is associated with an increased risk of diabetic retinopathy...

..Genetic variation in SIRT1 has been associated with body mass index (BMI) and risk of obesity. SIRT1 may be influenced by diet...

..3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility...

..This could impact the vitamin D signaling efficiency and might contribute to the increased fracture risk we observed for these risk haplotype alleles...

..We therefore investigated 5 polymorphisms in the TGF-beta1 gene (-800 G/A, -509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro, and codon 263 Thr/Ile) in relation to the risk of myocardial infarction and stroke in a population-based study...

..This suggests this polymorphism to play a minor role, if any, as a genetic determinant of osteoporosis in elderly subjects...

..5 year per A allele (12%); P = 2.5 × 10(-8)). These common genetic variants regulate timing of ovarian aging, an important risk factor for breast cancer, osteoporosis and cardiovascular disease...

..In the present study, we investigated whether the ER22/23EK polymorphism is associated with survival, cholesterol levels, and two predictors of mortality: serum C-reactive protein and interleukin 6 levels...

..Our findings expand previous similar findings in a Japanese study to whites and show a relationship with fracture risk of this functional polymorphism...

..Evidence suggests that genetic variations in the estrogen receptor alpha (ESR1) gene may influence IHD risk, but the role of common sequence variations in the ESR1 gene is unclear...

..Breast cancer development and progression are dependent on estrogen activity. In premenopausal women, estrogen production is mainly regulated through the hypothalamic-pituitary-gonadal (HPG) axis...

..Our findings suggest that this promoter polymorphism or another functional polymorphism in linkage disequilibrium may be a genetic determinant of BMD levels and rate of bone loss in postmenopausal women...

..To investigate whether polymorphisms in the estrogen receptor alpha (ESR1) and beta (ESR2) genes were a risk factor for open-angle glaucoma (OAG)...

..This effect is independent of age at menopause, time since menopause and BMI. These findings support the hypothesis that endogenous oestrogens may protect against cognitive decline with ageing...

..Consequently the age related increase of SHBG does not account for the age related decline in non-SHBG-T in healthy adult men...

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..Increased fracture risk in hyponatremia also was independent of recent falls, pointing toward a possible effect on bone quality...

..Substantial progress has been made that will deepen our understanding of variability in the vitamin D endocrine system and might find applications in risk assessment of disease and in predicting response-to-treatment...

..In women, early menopause, current smoking, and walking aid use are additional independent risk factors for incident vertebral fractures...

..04 mm, P = 0.02). We found that among type 2 diabetic patients, mean systolic blood pressure, pulse pressure, and risk of hypertension increased with the number of risk genotypes for the RAS genes and the salt sensitivity genes...

..CONCLUSION: Statin use is associated with a lower risk of vertebral fracture. Randomized clinical trials in a population at risk for fracture are needed to examine this association...

..The findings do not support the hypothesis that higher levels of endogenous estradiol reduce risk of dementia, neither in women nor in men...

..Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population...

..From infusion studies with radioactively labelled hormones, we know that oestradiol (E2) and oestrone (E1) are either directly secreted by the testes and adrenal glands or peripherally produced from testicular or adrenal androgens...

..The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD...

..The molecular mechanism underlying this association needs further study...

..We therefore hypothesized that mildly elevated homocysteine levels might be related to age-related osteoporotic fractures...

..To study the association between baseline vitamin D status, bone mineral density (BMD), and the development of radiographic osteoarthritis (ROA) of the knee in a large population-based cohort of men and women...

..These findings highlight the importance of considering nutritional factors in epidemiological studies of osteoporosis and fractures...

..Improvement of mobility may be an important factor in this finding and we therefore tested whether mobility tests improved after FRID withdrawal...

..Little is known about the role of AMH in human ovarian physiology. We hypothesize that in women AMH has a similar role in ovarian function as in mice and investigated this using a genetic approach...

..Eventually, results of this research will deepen our understanding of variability in the Vitamin D endocrine system and might find applications in risk-assessment of disease and in predicting response-to-treatment...

..We assessed the relation between the ACE I/D polymorphism and the risk of incident heart failure in normotensive and hypertensive subjects...

..Therefore, we conclude that in eugonadal men, higher SHBG levels are associated with lower levels of non-SHBG-E2 but slightly higher levels of non-SHBG-T. This means that SHBG cannot be regarded as an estrogen amplifier in eugonadal men...

..The TSHR-Asp727Glu polymorphism is associated with lower TSH levels. We therefore examined the association of this polymorphism with bone parameters...

..02 and p (trend) = 0.05, respectively). These data provide estimates of lipid heritability unbiased due to selection and suggest that this population represents a good opportunity to localize novel genes influencing plasma lipid levels...

..Our data suggest that carriers of the 22/23EK allele are relatively more resistant to the effects of GCs with respect to the sensitivity of the adrenal feedback mechanism than noncarriers, resulting in a better metabolic health profile...

..The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis...

..To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women...

..Taken together, the average hip fracture risk in men is much lower than in women but appeared to be similar at the same BMD. Therefore, we propose the use of the same absolute BMD thresholds for decisions about interventions...

..This IGF-I gene polymorphism in the promoter region of the IGF-I gene may directly influence the expression of IGF-I. In the present study we evaluated the role of this polymorphism in the age-related decline in serum IGF-I levels...

..In women, positive associations between levels of testosterone and aortic atherosclerosis were largely due to adverse cardiovascular disease risk factors...

..The ultimate goal of this approach is to identify the combinations of functional sequence variants that modulate the vitamin D endocrine system and confer risk of disease...

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..CONCLUSION: Our data do not support the hypothesis that higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes and better memory performance...

..In both genders, the incidence increases with age. Furthermore, the presence of a prevalent vertebral fracture and a low BMD are strong independent predictors of incident vertebral fractures in men and women...

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..This study demonstrated that serum ALP activity is a sensitive marker of PDB in men and women >55 years of age, but the majority of those affected have normal serum ALP activity...

..Recent studies suggested that this gene might have smoking-dependent effects on the development of cardiovascular disease...

..The decreased vertebral fracture risk in yr 4 alone was not different from that observed in the first 3 yr...

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..The aim of this study was to examine whether C-reactive protein (CRP) levels and CRP gene variations were associated with an altered risk of colorectal, lung, breast, or prostate cancer...

..We studied the association between polymorphisms in the estrogen receptor alpha (ERalpha) gene and the prevalence of radiographic OA of the knee...

..Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear...

..This lower risk disappeared approximately 4 months after thiazide use was discontinued. CONCLUSIONS: Thiazide diuretics protect against hip fracture, but this protective effect disappears within 4 months after use is discontinued...

..7, P = 0.001). We confirm that the COLIA1 Sp1 polymorphism influences BMD and the risk of fracture in postmenopausal Caucasian women. In contrast, we found no independent effect of the -1997 G/T promoter polymorphism on BMD or fracture...

..The results of this study suggest that in elderly women an association between especially lumbar spine BMD and incident breast cancer exists. Stimulating effects of estrogen on both trabecular bone and mammary cells may be responsible...

..10 to 2.10, p = 0.02). The risk of death increased with the number of variant alleles. Our study suggests that genetically determined low IGF-I activity is an important determinant of mortality in subjects with MI...

..Our results suggest that in elderly and late postmenopausal women hormonal factors do not predict quality of life...

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..44; P<0.0001), after adjustment for established cardiovascular risk factors. After exclusion of younger subjects from 2 cohorts, because of age interaction, the odds ratio increased (to 1.63)...

..Estrogen receptor alpha (ESR1) is a candidate gene for osteoporosis, but previous studies of ESR1 polymorphisms in this field were hampered by small sample size, lack of standardization, and inconclusive results...