-
[show abstract]
[hide abstract]
ABSTRACT: Objective:The aims of the study were to analyze whether there is an association between serum PTH and the prevalence of vertebral fractures and its possible dependence on vitamin D status, and to assess the influence of serum 25-hydroxyvitamin D (25OHD) in the relationship between PTH and bone mineral density (BMD) or bone turnover markers (BTMs).Design, Participants, and Setting:A total of 820 postmenopausal women were recruited after excluding those with any known condition that could influence serum PTH levels, except for a possible low serum 25OHD. Serum PTH and 25OHD concentrations, as well as vertebral fracture prevalence, BMD, and BTM (CTX and PINP) values were recorded. Serum PTH levels were divided into tertiles, and women were grouped into those in the highest tertile (>58 pg/ml) and those below. Serum 25OHD levels were stratified in 3 categories (<20, 20-30, and >30 ng/ml).Results:Vertebral fracture prevalence was greater in women with PTH above 58 pg/ml (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.04-2.84). After stratifying by 25OHD, this difference was only significant in women below 20 ng/ml (OR, 2.00; 95% CI, 1.02-3.87), those with 25OHD between 20 and 30 ng/ml showing a trend toward this (OR, 1.99; 95% CI, 0.92-4.36). Differences in BMD or BTM between women above and below 58 pg/ml of PTH were also observed only in those below 20 ng/ml.Conclusion:Elevated PTH levels are associated with increased prevalence of vertebral fractures, low bone mass, or higher BTM only in the presence of hypovitaminosis D. An adequate nutritional status in the vitamin appears to protect the bone from the deleterious effect of a high PTH.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Objective: The aims of the study were to analyze whether there is an association between serum PTH and the prevalence of vertebral fractures and its possible dependence on vitamin D status, and to assess the influence of serum 25-hydroxyvitamin D (25OHD) in the relationship between PTH and bone mineral density (BMD) or bone turnover markers (BTMs). Design, Participants, and Setting: A total of 820 postmenopausal women were recruited after excluding those with any known condition that could influence serum PTH levels, except for a possible low serum 25OHD. Serum PTH and 25OHD concentrations, as well as vertebral fracture prevalence, BMD, and BTM (CTX and PINP) values were recorded. Serum PTH levels were divided into tertiles, and women were grouped into those in the highest tertile (58 pg/ml) and those below. Serum 25OHD levels were stratified in 3 categories (20, 20 –30, and 30 ng/ml).
Journal of Clinical Endocrinology & Metabolism 01/2013; 98(4):1711-7. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Objective:Our objective was to know the extent to which a fall in bone turnover markers is influenced by serum 25-hydroxyvitamin D (25OHD) levels in patients on alendronate (ALN) treatment.Design, Participants, and Setting:A total of 140 postmenopausal osteoporotic women were randomized to receive either ALN or ALN plus 25OHD(3) (ALN+VitD) over a 3-month period. Serum 25OHD, PTH, C-terminal telopeptide of type I collagen (CTX), and amino-terminal propeptide of type I collagen (P1NP) were measured at baseline and at the end of the 3 months.Results:25OHD rose four times above baseline levels in the ALN+VitD group, whereas no changes were seen in the ALN group. Administering ALN resulted in a significant decline in both serum CTX (53 ± 24%) and P1NP (46 ± 19%). After ALN+VitD, the fall in CTX amounted to 61 ± 20% (P = 0.06 compared with ALN) and P1NP to 50 ± 23% (P = 0.35). When patients were divided into those below and above 20 ng/ml of baseline serum 25OHD, in those below, CTX decreased by 48 ± 26% in the ALN group and by 61 ± 17% in the ALN+VitD group (P = 0.015). For P1NP, the corresponding figures were 43 ± 20 and 50 ± 23% (P = 0.2). In patients above 20 ng/ml, no differences were seen regarding CTX (58 ± 21% decrease in the ALN group and 60 ± 23% in the ALN+VitD group; P = 0.7) or P1NP (49 ± 18 and 50 ± 20%; P = 0.9).Conclusions:Administration of 25OHD(3) is not an indispensable requirement for bisphosphonates to develop their bone antiresorptive effect. In fact, in patients with vitamin D sufficiency, no benefit is observed when the vitamin is added. However, in patients with vitamin D deficiency, an approximately 25% greater fall in the bone resorption marker CTX is seen with its administration.
The Journal of clinical endocrinology and metabolism 10/2012; · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Sirtuin 1, encoded by the SIRT1 gene, is an emerging modulator of carbohydrate and lipid metabolism and may also influence the differentiation of bone cells. Our objective was to test the hypothesis that polymorphisms of SIRT1 are associated with body mass index (BMI) and bone mineral density (BMD).
We carried out a cross-sectional genetic association study with genotyping of ten single nucleotide polymorphisms of the SIRT1 region. The discovery cohort included 1394 individuals (342 males, 1052 females). Significant results were replicated in an independent cohort of 408 males.
We did not find a significant association of genotypes with BMD. There were also no significant BMI differences across genotypes in females. However, in males, two polymorphisms tended to be associated with BMI in the discovery cohort (p 0.03 and 0.05). A similar trend was also observed in the replication cohort. Thus, in the combined analysis of both cohorts, males with C alleles at the rs12049646 locus had a lower BMI than TT homozygotes, with a mean difference of 0.82 kg/m(2) (95% confidence interval 0.15-1.48; p = 0.016). Differences in the DNA binding of nuclear proteins between C and T alleles were also observed in vitro.
These results suggest that common variants of the SIRT1 gene influence BMI but not BMD.
Archives of medical research 07/2012; 43(5):363-8. · 1.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Primary hyperparathyroidism (PHPT) affects mainly cortical bone. It is thought that parathyroid hormone (PTH) indirectly regulates the activity of osteoclasts by means of the osteoprotegerin/ligand of the receptor activator of nuclear factor-κβ (OPG/RANKL) system. Several studies have confirmed that OPG (osteoprotegerin) and RANKL (ligand of the receptor activator of nuclear factor-κβ) loci are determinants of bone mineral density (BMD) in the general population. The aim of this study is to analyze the relationship between fractures and BMD and the rs3102735 (163 A/G), rs3134070 (245 T/G) and rs2073618 (1181 G/C) SNPs of the OPG and the rs2277438 SNP of the RANKL, in patients with sporadic PHPT.
We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analyzed anthropometric data, history of fractures or renal lithiasis, biochemical determinants including markers for bone remodelling, BMD measurements in the lumbar spine, total hip, femoral neck and distal radius, and genotyping for the SNPs to be studied.
Regarding the age of diagnosis, BMI, menopause status, frequency of fractures or renal lithiasis, we found no differences between genotypes in any of the SNPs studied in the PHPT group. Significant lower BMD in the distal radius with similar PTH levels was found in the minor allele homozygotes (GG) compared to heterozygotes and major allele homozygotes in both OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs in those with PHPT compared to control subjects. We found no differences between genotypes of the OPG rs2073618 (1181 G/C) SNP with regard to BMD in the PHPT subjects. In the evaluation of rs2277438 SNP of the RANKL in PHPT patients, we found a non significant trend towards lower BMD in the 1/3 distal radius and at total hip in the minor allele homocygotes (GG) genotype group versus heterocygotes and major allele homocygotes (AA).
Our study provides the first evaluation of the relationship between SNPs of the OPG/RANK system and sporadic PHPT. Subjects with PHPT and minor homocygote genotype (GG) for the OPG rs3102735 (163 A/G) and OPG rs3134070 (245 T/G) SNPs have lower BMD in the distal radius, and this association does not appear to be mediated by differences in PTH serum levels.
BMC Medical Genetics 12/2011; 12:168. · 2.33 Impact Factor
-
José A Riancho,
Yongjun Liu,
Jesús Sainz,
Miguel A García-Pérez,
José M Olmos,
Alfonso Bolado-Carrancio, Carmen Valero,
Javier Pérez-López,
Antonio Cano,
Tielin Yang,
Carolina Sañudo,
Hong-Wen Deng,
José C Rodríguez-Rey
[show abstract]
[hide abstract]
ABSTRACT: There is growing evidence for a link between energy and bone metabolism. The nuclear receptor subfamily 5 member A2 (NR5A2) is involved in lipid metabolism and modulates the expression of estrogen-related genes in some tissues. The objective of this study was to explore the influence of NR5A2 on bone cells and to determine whether its allelic variations are associated with bone mineral density (BMD).
Analyses of gene expression by quantitative PCR and inhibition of NR5A2 expression by siRNAs were used to explore the effects of NR5A2 in osteoblasts. Femoral neck BMD and 30 single nucleotide polymorphisms (SNPs) were first analyzed in 935 postmenopausal women and the association of NR5A2 genetic variants with BMD was explored in other 1284 women in replication cohorts.
NR5A2 was highly expressed in bone. The inhibition of NR5A2 confirmed that it modulates the expression of osteocalcin, osteoprotegerin, and podoplanin in osteoblasts. Two SNPs were associated with BMD in the Spanish discovery cohort (rs6663479, P=0.0014, and rs2816948, P=0.0012). A similar trend was observed in another Spanish cohort, with statistically significant differences across genotypes in the combined analysis (P=0.03). However, the association in a cohort from the United States was rather weak. Electrophoretic mobility assays and studies with luciferase reporter vectors confirmed the existence of differences in the binding of nuclear proteins and the transcriptional activity of rs2816948 alleles.
NR5A2 modulates gene expression in osteoblasts and some allelic variants are associated with bone mass in Spanish postmenopausal women.
European Journal of Endocrinology 11/2011; 166(1):69-75. · 3.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To compare bone parameters measured by calcaneous quantitative ultrasonography (BUS) in subjects with and without metabolic syndrome (MetS). In addition, we wanted to examine the association of each of the individual components of the syndrome with BUS measurements, to study the relationship between calciotropic hormones or bone turnover markers with BUS parameters in subjects with or without MetS, and to explore the possibility that the relationship between prevalent vertebral and non-vertebral fractures and BUS is influenced by MetS status.
Cross-sectional study.
We investigated 1209 (421 men and 788 women) participants from the Camargo Cohort Study. Prevalence of MetS was 27% in men and 31% in women. Women, but not men, with MetS had higher age-adjusted BUS parameters compared with those without (p<0.05), the difference disappearing after adjustment for BMI. Out of the five single components of MetS, only waist perimeter was significantly associated with BUS (p<0.01), the association being restricted to women. In men and women with MetS (but not without) a positive significant association was observed between BUS and 25OHD levels. BUS parameters were associated with serum P1NP or CTX in normal women, but not in those with MetS. Prevalent vertebral and non-vertebral fractures and BUS parameters (BUA and SOS, respectively) are inversely associated, but this relationship, however, is not influenced by MetS status.
BUS parameters are higher in women with MetS, and this difference disappears after adjusting for BMI. MetS status did not influence the relationship between BUS parameters and vertebral or non-vertebral fractures.
Maturitas 03/2011; 69(2):162-7. · 2.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Secreted frizzled-related protein and sclerostin, encoded by FRZB and SOST genes, respectively, are extracellular Wnt inhibitors that tend to decrease bone formation. The purpose of this study was to explore the association of the sets of polymorphisms capturing common variations of these genes with bone mineral density (BMD).
Twelve polymorphic loci of the FRZB gene and 7 of the SOST gene were genotyped in postmenopausal women from two Spanish regions (Cantabria, n = 1043, and Valencia, n = 342). The polymorphisms included tagging single nucleotide polymorphisms and single nucleotide polymorphisms with possible functional consequences assessed in silico.
The rs4666865 polymorphism of the FRZB gene was associated with spine BMD in the Cantabria cohort in the single-locus (P = 0.008) and the haplotypic analysis. However, the results were not replicated in the Valencia cohort. Several polymorphisms at the 5' region of the SOST gene and, particularly, rs851056 were associated with BMD in women from both cohorts (P = 0.002 in Cantabria and P = 0.005 in Valencia). When the results of both cohorts were combined, the mean (SD) BMD difference across rs851056 genotypes was 47 (0.31) mg/cm(2) (P < 0.001). No differences in FRZB and SOST expression in femoral trabecular bone tissue were detected across genotypes.
Polymorphisms in the 5' region of SOST gene are associated with BMD in postmenopausal women. They may contribute to explain, in part, the hereditary influence on bone mass.
Menopause (New York, N.Y.) 03/2011; 18(7):802-7. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate bone mineral density (BMD) and bone metabolism in hypertensive postmenopausal women, and to differentiate the effect of thiazides from that of other antihypertensive agents.
A community-based population of 636 postmenopausal women, 293 with hypertension (160 receiving thiazides, and 133 receiving other antihypertensive treatments), and 343 control women, were evaluated. Serum levels of aminoterminal propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (beta-CTX), 25-hydroxivitamin D, and intact parathyroid hormone were measured by electrochemiluminiscence. BMD was determined by DXA, and heel quantitative ultrasound measurements (QUS) with a gel-coupled device.
BMD expressed as Z-score was higher in both groups of hypertensive women at all locations. Expressed as g/cm(2), it was also higher in patients on thiazides at femoral neck and lumbar spine. Only in the latter site, differences remained significant after adjusting for potential confounding variables, including BMI. Bone turnover markers were lower in both groups of hypertensive women, although the difference was greater in those on thiazides. After adjusting for potential confounders, differences remained significant only in the thiazide group.
Our results add evidence to the idea that thiazides are beneficial to prevent bone loss.
Maturitas 04/2010; 65(4):396-402. · 2.77 Impact Factor
-
Journal of Neurology 03/2010; 257(3):488-9. · 3.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Objectives: The aims of this study were to compare in participants with and without metabolic syndrome (1) bone mineral density (BMD), (2) prevalent vertebral and nonvertebral fractures, and (3) calciotropic hormones and bone turnover markers and to examine the association of each component of metabolic syndrome with bone parameters. Methods: A cross-sectional study (495 men and 1,013 women) from the Camargo Cohort Study was conducted. A multivariable regression approach was used to analyze the relationship between the components of metabolic syndrome and bone parameters. Results: Women with metabolic syndrome had higher age-adjusted BMD at all localizations (P G 0.0001) than did women without metabolic syndrome. Adjusting for body mass index canceled out this difference at the spine and femoral neck, although borderline significance persisted at the total hip. Moreover, in regression analyses, waist circumference (P G 0.0001) and hypertension (P between 0.002 and G0.0001) highly correlated with BMD at the three sites. However, no significant differences in BMD were found in men between those with and without metabolic syndrome. No differences in the prevalence of vertebral or nonvertebral fractures between participants with metabolic syndrome and controls were found for either sex. 25-Hydroxyvitamin D was significantly lower (P G 0.0001) and parathyroid hormone was significantly higher (P G 0.0001) in women with metabolic syndrome than in women without metabolic syndrome, whereas no differences were seen in men. Propeptide of type I collagen and C-terminal telopeptide of type I collagen were significantly lower in participants with metabolic syndrome than in controls in either sex. Conclusions: Women with metabolic syndrome show higher BMD than controls do, mainly driven by their higher body weight. Bone remodeling in these women is lower. Despite the greater bone mass and lower bone turnover, fracture prevalence is not reduced, suggesting worse bone quality and/or higher tendency to fall. No differences in BMD or fractures were seen in men, suggesting that the impact of metabolic syndrome on bone is sex dependent.
Menopause 01/2010; 17(5):955-961. · 3.76 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This cross-sectional study was performed to determine the reference ranges for two bone turnover markers--aminoterminal propeptide of type I collagen (P1NP) and C-terminal telopeptide of type I collagen (beta-CrossLaps, beta-CTX)--in normal postmenopausal Spanish women as determined in serum by automated methods.
A community-based population of 1080 healthy postmenopausal women was evaluated. Data regarding risk factors for osteoporosis and fractures were collected by means of a structured questionnaire. Fasting serum levels of P1NP, beta-CTX, 25-Hydroxivitamin D (25OHD), and intact parathyroid hormone (iPTH) were measured on the Elecsys 2010 automated analyzer (Roche). BMD at lumbar spine, femoral neck and total hip was determined by DXA.
The mean age of subjects was 63+/-9. Logarithmic transformation of both markers was performed to allow for normal distributions. Mid-95% ranges for P1NP and beta-CTX were 19-100 ng/ml and 0.112-1.018 ng/ml, respectively. Mean values of P1NP (47.7+/-19.9 ng/ml) were similar to those previously determined by the manufacturer of the assays, whereas beta-CTX mean values (0.387+/-0.197 ng/ml) were lower. Both markers were higher among osteoporotic women.
Values obtained from this well-characterized population study provide reference ranges for serum automated P1NP and beta-CTX in normal Spanish postmenopausal women.
Clinica chimica acta; international journal of clinical chemistry 10/2009; 409(1-2):70-4. · 2.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There is growing evidence of a link between lipid and bone metabolism, although data on this association in European men are scarce. This cross-sectional study from a community-based prospective cohort aims to explore the association of serum lipids with different aspects of bone metabolism in Spanish men. Demographic and anthropometric measurements, biochemical parameters including serum lipids, bone remodelling markers and calciotropic hormones, bone mineral density (BMD) assessed by dual X-ray absorptiometry and heel quantitative ultrasound, and prevalent vertebral and non-vertebral fractures, were evaluated in 289 men. Calciotropic hormones or bone markers were not associated with serum lipids. Serum total (TC) and LDL cholesterol, as well as LDL/HDL ratio were positively correlated to BMD at lumbar spine and hip. No significant correlation was noted for triglycerides or HDL. We observed a positive association between triglycerides, LDL/HDL ratio and BUA, and between TC/HDL ratio and both, QUI and BUA. BMD at the femoral neck and total hip was significantly higher in men with hypercholesterolemia after controlling for all the covariates (p=0.007). We did not observe any association between serum lipids and prevalent vertebral fractures. However, we found that TC (p=0.03) and LDL (p=0.04) were lower in subjects with non-vertebral fractures. In conclusion, we have found that a more unfavorable lipid profile (mainly higher LDL-C levels) is associated with higher BMD at lumbar spine and hip in Spanish men. Moreover, we did not observe any association between hypercholesterolemia and prevalent vertebral fractures, but we found lower serum TC and LDL-C levels in men with prevalent non-vertebral fractures.
Endocrine Journal 10/2009; 57(1):51-60. · 2.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BMD has a strong heritable component. Estrogen activity depends on the aromatization of androgenic precursors in nongonadal tissues both in postmenopausal women and men. Therefore, aromatase is an appealing candidate gene to explain, in part, the genetic component of BMD. In fact, an association between aromatase polymorphisms and BMD has been previously reported in some relatively small groups. In this study, we explored the relationship between several SNPs in the aromatase region and hip BMD in 1163 postmenopausal women. We found significant differences across genotypes, particularly in older women. The BMD differences between homozygous women with opposing genotypes were 4.2% in the whole group and 7.3% in women >67 yr of age. Body weight was significantly associated with BMD also, but there was no evidence for a statistically significant interaction between body weight and aromatase polymorphisms. Electrophoretic mobility shift assays suggested the binding of the CEBPβ transcription factor to the C/G rs1062033 locus, located ∼12 kb upstream of the translation start site. Experiments of transient transfection of osteoblastic cells with luciferase reporters showed differences in the transcriptional activity of alleles C and G at this locus, with different responses to the co-transfection of a CEBPβ expression vector. Furthermore, evidence for differential allelic expression was found in bone tissue samples. In conclusion, polymorphisms in a 12-kb region of the aromatase gene are associated with BMD in postmenopausal women, particularly during the late postmenopausal period. In vitro functional studies point to rs1062033 as a true regulatory polymorphism.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 09/2009; 24(10):1709 - 1718. · 6.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the time course of bone mineral density (BMD) in women with anorexia nervosa (AN) during 2-year follow-up.
We prospectively studied 51 female with AN aged 18-38 years, and 40 age-matched healthy women (19-34 years). BMD was measured in lumbar spine (LS), femoral neck (FN), and total hip (TH) by DXA.
At baseline, weight, body mass index, and lumbar and hip BMD were significantly (p < .001) lower in AN patients than in controls. Patients who gain weight showed a significant increase in BMD at FN (+1.6%; p < .05), and TH (+4.4%; p < .05) and lower nonsignificant changes in LS (+1.3%). Weight at entry, and percent change of weight were significant determinants (p < .05) of the variability in percent change of BMD at FN and TH, whereas weight at entry was the main determinant of bone modifications at lumbar spine.
Our data emphasize the influence of weight gain in recovery of bone mass in AN patients, especially at the hip.
International Journal of Eating Disorders 08/2009; 43(6):537-42. · 2.95 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BMD has a strong heritable component. Estrogen activity depends on the aromatization of androgenic precursors in nongonadal tissues both in postmenopausal women and men. Therefore, aromatase is an appealing candidate gene to explain, in part, the genetic component of BMD. In fact, an association between aromatase polymorphisms and BMD has been previously reported in some relatively small groups. In this study, we explored the relationship between several SNPs in the aromatase region and hip BMD in 1163 postmenopausal women. We found significant differences across genotypes, particularly in older women. The BMD differences between homozygous women with opposing genotypes were 4.2% in the whole group and 7.3% in women >67 yr of age. Body weight was significantly associated with BMD also, but there was no evidence for a statistically significant interaction between body weight and aromatase polymorphisms. Electrophoretic mobility shift assays suggested the binding of the CEBPss transcription factor to the C/G rs1062033 locus, located approximately 12 kb upstream of the translation start site. Experiments of transient transfection of osteoblastic cells with luciferase reporters showed differences in the transcriptional activity of alleles C and G at this locus, with different responses to the co-transfection of a CEBPss expression vector. Furthermore, evidence for differential allelic expression was found in bone tissue samples. In conclusion, polymorphisms in a 12-kb region of the aromatase gene are associated with BMD in postmenopausal women, particularly during the late postmenopausal period. In vitro functional studies point to rs1062033 as a true regulatory polymorphism.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2009; 24(10):1709-18. · 6.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Estrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the SHBG gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures.
Four biallelic polymorphisms of the SHBG gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA.
Age, body weight, and two polymorphisms of the SHBG gene (rs6257 and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the strongest association with serum SHBG (p=0.0004). The difference in SHBG levels between women with AA and GG genotypes at the rs1799941 locus was 39%. There were no significant differences in BMD across SHBG genotypes. The genotypes showed similar frequency distributions in control women and women with vertebral or hip fractures.
Some common genetic variants of the SHBG gene, and particularly an A/G polymorphism situated in the 5' region, influence serum SHBG levels. However, a significant association with BMD or osteoporotic fractures has not been demonstrated.
BMC Medical Genetics 01/2009; 9:112. · 2.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Klotho gene codes for a protein with glucuronidase activity and is thought to influence bone and vascular homeostasis. We studied the relationship of a common T/G polymorphism, resulting in a phenylalanine (F) to valine (V) substitution at aminoacid position 352, with bone mineral density (BMD) and osteoporotic fractures. The study group comprised 914 Spanish women, including 438 control subjects, 190 patients with osteoporosis, 198 with hip fractures, and 88 patients with severe osteoarthritis. BMD was measured by DEXA in 540 women from the control and osteoporosis groups. Allele frequencies were 86% and 14%, for the F and V alleles, respectively. In comparison with the most common FF genotype, postmenopausal women with FV/VV genotypes had higher hip BMD (femoral neck: 0.673 +/- 0.011 vs. 0.644 +/- 0.006 g/cm(2); P = 0.02; total hip: 0.807 +/- 0.014 vs. 0.774 +/- 0.008 g/cm(2); P = 0.03). Klotho alleles explained about 1.5% of BMD variance, but were not associated to the risk of osteoporotic spine or hip fractures. The Klotho genotype was not associated to BMD in premenopausal women. In conclusion, the F352V Klotho polymorphism is associated with BMD in postmenopausal women, suggesting that Klotho gene variants influence skeletal aging.
Biogerontology 05/2007; 8(2):121-7. · 3.34 Impact Factor
-
Medicina Clínica 04/2007; 128(9):355. · 1.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Osteoporosis has a significant genetic component. The aromatase-dependent conversion of androgenic precursors is the main source of estrogens in postmenopausal women.
The objective of the investigation was to study the relationship of a set of single nucleotide polymorphisms (SNPs) of the aromatase gene with osteoporosis and determine their functional influence on gene transcription. DESIGN, PARTICIPANTS, AND METHODS: This was a case-control study including 135 women with vertebral fractures due to postmenopausal osteoporosis and 312 controls. Alleles at four SNPs situated between exons I.2 and 3 were determined by Taqman assays. Total aromatase RNA and differential allelic-specific expression were studied by RT-real time PCR in adipose tissue samples taken from 50 individuals.
The SNPs studied were in strong linkage disequilibrium. A common haplotype, present in about half of the population, was identified as being associated with an increased risk of fractures (odds ratio 1.8, 95% confidence interval 1.2-2.8, P = 0.006). There was evidence of differential allelic expression. In heterozygous individuals, transcripts bearing T alleles at rs700518 SNP (which were included in the risk haplotype) were less abundant than those with the alternative C alleles (P < 0.001). Total aromatase expression was four times lower in fat samples from individuals who were homozygotes for the unfavorable alleles than in the opposite homozygotes (P = 0.007).
A common haplotype of aromatase associated with gene expression is also associated with the risk of osteoporotic vertebral fractures in postmenopausal women. These data are in line with the hypothesis that the aromatase-dependent synthesis of estrogens plays an important role in bone homeostasis in postmenopausal women.
Journal of Clinical Endocrinology & Metabolism 02/2007; 92(2):660-5. · 6.50 Impact Factor
