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- Michaëlsson, Karl, et al.
(författare)
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The positive effect of dietary vitamin D intake on bone mineral density in men is modulated by the polyadenosine repeat polymorphism of the vitamin D receptor
- 2006
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 39:6, s. 1343-1351
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Few studies have considered the dietary influence of vitamin D intake on bone mineral density (BMD). Numerous studies have examined the association between VDR polymorphism and BMD, but no previous study has examined the joint influence of dietary vitamin D intake and VDR polymorphism on BMD. METHODS: We therefore conducted a study in 230 men aged 41-76 years of age. BMD was measured with DXA. A second bone scan was performed on average 2.7 years after the first investigation. Dietary habits were assessed by 14 dietary 24-h recall interviews. The polyadenosine (A) VDR genotypes were determined. RESULTS: Dietary vitamin D intake was associated with BMD at all sites, also after multivariate adjustment. Those in the highest quintile of intake had 9% higher femoral neck BMD (p = 0.004), 6% higher BMD at the lumbar spine (p = 0.06) and 5% higher total body BMD (p = 0.003) compared to men in the lowest quintile of dietary vitamin D intake. However, the positive association between vitamin D intake and BMD was especially apparent among those with the L/L polyadenosine (A) VDR genotype explaining between 10 and 15% of the variability in BMD depending on site (p < 0.004). There was furthermore a trend, in the lumbar spine, of less reduction in BMD with increasing vitamin D intake (p = 0.07) but not at the other sites. Calcium intake conferred no association with BMD. CONCLUSIONS: Our results indicate that the extent of positive association between dietary vitamin D intake and BMD in men is dependent on VDR polymorphism, a novel conceivable important gene-environmental interaction.
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| 2. |
- Stiger, Fredrik, et al.
(författare)
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Association between repeat length of exon 1 CAG microsatellite in the androgen receptor and bone density in men is modulated by sex hormone levels
- 2008
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 82:6, s. 427-35
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Tidskriftsartikel (refereegranskat)abstract
- In this study we examined whether the androgen receptor (AR) gene CAG repeat polymorphism and serum androgen levels are associated with bone mineral density (BMD) and changes in BMD during 2-3 years in 229 healthy men 41-76 years old. Microsatellite analysis was performed on an automated sequencer. Indices of bioavailable testosterone (free testosterone [FT] and free androgen index) were calculated. BMD was measured using both dual-energy Xray absorptiometry and quantitative ultrasound. All participants completed a questionnaire regarding major possible osteoporosis risk factors. In linear regression analysis there was a modest positive association, which was independent of age and body mass index (BMI), between AR repeat length and BMD at all sites. Although this association was significant independent of BMI, analyses in the subgroup of obese men (BMI > 30) did not reach significance, while the effect was enhanced when analyzing only nonobese men (BMI < or = 30). There was no association between the AR gene polymorphism and rate of bone loss, FT, and BMD or testosterone and bone loss. Interestingly, the association between AR and BMD was modified by total testosterone. The lowest age- and BMI-adjusted average femoral neck BMD was found among men in the lowest tertile for both AR repeat length and FT, whereas men within the higher categories of these variables displayed the highest BMD. In conclusion, there is a positive association between the AR CAG repeat polymorphism and BMD, which is modified by androgen levels in healthy men.
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| 3. |
- Wedrén, Sara, et al.
(författare)
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Associations between androgen and Vitamin D receptor microsatellites and postmenopausal breast cancer
- 2007
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 16:9, s. 1775-1783
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the association between polymorphism in the androgen receptor (AR) and vitamin D receptor (VDR) genes and breast cancer risk in a large population-based case-control study of genetically homogenous Swedish women. We successfully determined both AR CAG(n) and VDR A(n) genotype in 1,502 women with invasive breast cancer and in 1,510 control women. We did not find any associations between AR or VDR microsatellite lengths and breast cancer when we used a priori determined cutoffs (/=22 repeats for AR and /=19 for VDR) to define long and short alleles. There was statistically significant interaction between VDR genotype and parity, such that women with two short alleles had a halved risk for breast cancer, irrespective of parity, compared with nulliparous women with two long alleles. Homozygosity for the long VDR allele was associated with a more advanced clinical stage at diagnosis. In exploratory analyses, we determined cutoffs based on visual inspection of distributions of allele lengths among cases and controls and found that women carrying two alleles with <20 AR CAG(n) repeats had an increased risk for breast cancer, odds ratio of 1.67 (95% confidence interval, 1.17-2.38), compared with those with two alleles with >/=20 repeats. Women carrying two VDR alleles with <21 A(n) were also at an increased risk, odds ratio of 1.26 (95% confidence interval, 1.04-1.51). Our data do not support major roles for AR or VDR polymorphism as breast cancer risk factors. However, we did find an interaction between VDR genotype and parity that remains to be corroborated.
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| 4. |
- Wedrén, Sara, et al.
(författare)
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Estrogen receptor alpha gene polymorphism and endometrial cancer risk : a case-control study
- 2008
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 8, s. 322-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Estrogen is an established endometrial carcinogen. One of the most important mediators of estrogenic action is the estrogen receptor alpha. We have investigated whether polymorphic variation in the estrogen receptor alpha gene (ESR1) is associated with endometrial cancer risk. METHODS: In 702 cases with invasive endometrial cancer and 1563 controls, we genotyped five markers in ESR1 and used logistic regression models to estimate odds ratios (OR) and 95 percent confidence intervals (CI). RESULTS: We found an association between rs2234670, rs2234693, as well as rs9340799, markers in strong linkage disequilibrium (LD), and endometrial cancer risk. The association with rs9340799 was the strongest, OR 0.75 (CI 0.60-0.93) for heterozygous and OR 0.53 (CI 0.37-0.77) for homozygous rare compared to those homozygous for the most common allele. Haplotype models did not fit better to the data than single marker models. CONCLUSION: We found that intronic variation in ESR1 was associated with endometrial cancer risk.
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