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An Sp1 binding site polymorphism in the COLIA1 gene predicts osteoporotic fractures in both men and women.

https://arctichealth.org/en/permalink/ahliterature204582
Source
J Bone Miner Res. 1998 Sep;13(9):1384-9
Publication Type
Article
Date
Sep-1998
Author
B L Langdahl
S H Ralston
S F Grant
E F Eriksen
Author Affiliation
Aarhus Bone and Mineral Research Group, University Department of Endocrinology, Aarhus University Hospital, Denmark.
Source
J Bone Miner Res. 1998 Sep;13(9):1384-9
Date
Sep-1998
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Biological Markers - analysis
Bone Density - genetics
Case-Control Studies
Collagen - genetics
Denmark - epidemiology
Female
Humans
Male
Middle Aged
Osteoporosis - complications - epidemiology - genetics
Polymerase Chain Reaction
Polymorphism, Genetic - genetics
Predictive value of tests
Regression Analysis
Sex Factors
Spinal Fractures - epidemiology - etiology - genetics
Abstract
Genetic factors play an important role in the pathogenesis of osteoporosis, and recent studies have shown that a polymorphic Sp1 binding site in collagen type I alpha1 (COLIA1) gene is associated with bone mass and vertebral fractures in women from the U.K. Information on the predictive value of the COLIA1 Sp1 polymorphism in other populations is limited, however, and no studies have yet been performed in osteoporotic males. In view of this, we analyzed COLIA1 genotypes in relation to bone density and biochemical markers of bone turnover and the presence of osteoporotic fractures in a case-control study of Danish men and women. COLIA1 genotype was determined by polymerase chain reaction analysis of genomic DNA extracted from peripheral blood samples and related to bone mass, biochemical markers of bone turnover, and the presence of fracture in a study of 375 osteoporotic vertebral fracture patients and normal controls. There was no significant effect of COLIA1 genotype on bone mass or biochemical markers when data from the control group (n = 195) and fracture group (n = 180) were analyzed separately. However, the genotype distribution was significantly different in the fracture cases compared with age-matched controls (chi2 = 16.48, n = 249,p = 0.0003) due mainly to over-representation of the ss genotype in the fracture patients (14.3% vs. 1.4%), equivalent to an odds ratio for vertebral fracture of 11.83 (95% confidence interval 2.64-52.97) in those with the ss genotype. Similar differences in genotype distribution between osteoporotic patients and controls were observed in both men (chi2 = 11.52, n = 95, p = 0.0032, OR = 2.04) and women (chi2 = 6.90, n = 154, p = 0.032, OR = 1.37). In keeping with the above, logistic regression analysis showed that the ss genotype was an independent predictor of osteoporotic fracture (p = 0.028). This study confirms that the COLIA1 Sp1 polymorphism is significantly associated with osteoporotic vertebral fractures. The association is seen in both men and women, and the effect on fracture risk appears to be partly independent of bone mineral density. Our results raise the possibility that genotyping at the Sp1 site could be of clinical value in identifying individuals at risk of osteoporotic fractures in both genders.
PubMed ID
9738510 View in PubMed
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Association and linkage disequilibrium analyses suggest genetic effects of estrogen receptor alpha and collagen IA1 genes on bone mineral density in Caucasian women.

https://arctichealth.org/en/permalink/ahliterature183256
Source
Calcif Tissue Int. 2003 Jun;72(6):643-50
Publication Type
Article
Date
Jun-2003
Author
R. Sapir-Koren
G. Livshits
E. Kobyliansky
Author Affiliation
Research Unit-Human Population Biology, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, 69978 Israel.
Source
Calcif Tissue Int. 2003 Jun;72(6):643-50
Date
Jun-2003
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Bone Density - genetics
Collagen Type I - genetics
Estrogen Receptor alpha
European Continental Ancestry Group - genetics
Female
Fingers - radiography
Haplotypes - genetics
Humans
Linkage Disequilibrium - genetics
Male
Middle Aged
Nuclear Family
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Receptors, Estrogen - genetics
Russia
Abstract
Estrogen receptor alpha (ER alpha) and collagen IA1 (COLIA1) genes have been suggested as possibly implicated in reduced bone mineral density (BMD). The present study investigated the occurrence of association and linkage disequilibrium between radiographic hand BMD and polymorphic alleles of ER alpha and COLIA1 genes, in human pedigrees of a Chuvasha population in Russia. The study sample included 463 members of 113 pedigrees, mostly nuclear families. We performed association and transmission disequilibrium test (TDT) analyses of the combined PvuII and XbaI RFLPs alleles on the same chromosome (haplotype) of the ER alpha gene with BMD Z scores of cancellous or cortical bone in the hand phalanges. The association analyses were performed separately for both genders in the parental generation, i.e., 'fathers' (n = 114; average age 64.2 y) and 'mothers' (n = 122; average age 62.7 y). The Px haplotype was associated significantly with lower BMD Z scores in 'mothers' only. The difference between subjects who carried one or two copies of the Px haplotype and those lacking it was 0.68 Z scores, P = 0.003 and 0.51 Z scores, P = 0.025 for cancellous and cortical bone, respectively. Multiple linear regression model with age, height, weight, and Px haplotype status as predictors explained 26.7% and 28.3% of the total observed variance in BMD with Px haplotype as independent predictor explaining 5.9%; P = 0.002 and 3%; P = 0.028 (cancellous and cortical bone, respectively). Results of t-TDT for triads of two parents and just one of their female offspring (but not male offspring) suggested the existence of linkage disequilibrium between the two loci of Px haplotype and BMD trait (P = 0.047). No association was found between polymorphic alleles of COLIA1 gene and BMD, but 'mothers' with combined genotypes of Px haplotype of ER alpha gene and "s" allele of COLIA1 gene had the lowest mean Z scores (-0.944 and -0.788 for cancellous and cortical bone, respectively). We conclude that the Px haplotype of the ER alpha gene is associated with low BMD values in females, as the phenotype is gender dependent (the association was not observed in males), and the "s" allele of COLIA1 gene in combination with this haplotype contributes to reduced BMD.
PubMed ID
14562991 View in PubMed
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Association with replication between estrogen-related receptor gamma (ESRRgamma) polymorphisms and bone phenotypes in women of European ancestry.

https://arctichealth.org/en/permalink/ahliterature148032
Source
J Bone Miner Res. 2010 Apr;25(4):901-11
Publication Type
Article
Date
Apr-2010
Author
Latifa Elfassihi
Sylvie Giroux
Alexandre Bureau
Nathalie Laflamme
David Ec Cole
François Rousseau
Author Affiliation
Centre de Recherche de l'Hôpital St-François d'Assise du Centre Hospitalier Universitaire de Québec, Quebec, Canada.
Source
J Bone Miner Res. 2010 Apr;25(4):901-11
Date
Apr-2010
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Bone Density - genetics
Estrogen Replacement Therapy
Female
Femur Neck - pathology - ultrasonography
Genetic Association Studies - statistics & numerical data
Genetic Predisposition to Disease
Haplotypes
Heel - pathology - ultrasonography
Humans
Lumbar Vertebrae - pathology - ultrasonography
Middle Aged
Ontario - epidemiology
Osteoporosis - epidemiology - genetics - ultrasonography
Phenotype
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Quebec - epidemiology
Receptors, Estrogen - genetics
Abstract
Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor gamma (ESRRgamma) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRRgamma sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20 kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRRgamma in the determination of bone density in women.
PubMed ID
19821770 View in PubMed
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Body composition and bone mineral density in children with premature adrenarche and the association of LRP5 gene polymorphisms with bone mineral density.

https://arctichealth.org/en/permalink/ahliterature148293
Source
J Clin Endocrinol Metab. 2009 Nov;94(11):4144-51
Publication Type
Article
Date
Nov-2009
Author
Pauliina Utriainen
Jarmo Jääskeläinen
Anne Saarinen
Esko Vanninen
Outi Mäkitie
Raimo Voutilainen
Author Affiliation
Departments of Pediatrics, University of Kuopio and Kuopio University Hospital, FI-70211 Kuopio, Finland. pauliina.utriainen@uku.fi
Source
J Clin Endocrinol Metab. 2009 Nov;94(11):4144-51
Date
Nov-2009
Language
English
Publication Type
Article
Keywords
Adrenarche - genetics
Body Composition
Bone Density - genetics
Child
Cross-Sectional Studies
Female
Femur Neck - anatomy & histology
Finland
Humans
LDL-Receptor Related Proteins - genetics
Low Density Lipoprotein Receptor-Related Protein-5
Male
Pituitary Gland - growth & development
Polymorphism, Genetic
Reference Values
Spine - anatomy & histology
Abstract
Precocious increase in adrenal androgen production is the hallmark of premature adrenarche (PA). Adrenal androgens have anabolic properties.
The objective of the study was to test whether body composition and bone mineral density (BMD) are altered in PA and study whether genetic variation in low-density lipoprotein receptor-related protein 5 (LRP5) affects BMD in PA.
This was a cross-sectional study.
The study was conducted at a university hospital.
The study included 126 prepubertal children (64 with PA, 10 boys; 62 non-PA controls, 10 boys). Femoral neck and lumbar spine areal and calculated volumetric BMD (dual energy X-ray absorptiometry), body composition (bioimpedance), serum 25-hydroxyvitamin D, and markers of bone turnover and calcium homeostasis were compared between the PA and control groups. Single-nucleotide polymorphisms of LRP5 were determined and associated with BMD.
Children with PA had higher femoral neck and lumbar spine BMD(areal) than the controls (Z-score 0.56 vs. -0.09, P
PubMed ID
19789208 View in PubMed
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Bone mineral density is associated with estrogen receptor gene polymorphism in men.

https://arctichealth.org/en/permalink/ahliterature191578
Source
Anthropol Anz. 2001;59(4):343-53
Publication Type
Article
Date
2001
Author
R. Sapir-Koren
G. Livshits
T. Landsman
E. Kobyliansky
Author Affiliation
Research Unit-Human Population Biology, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv-University, Ramat Aviv, Israel.
Source
Anthropol Anz. 2001;59(4):343-53
Date
2001
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Aged
Aged, 80 and over
Bone Density - genetics
Estrogen Receptor alpha
Female
Genotype
Haplotypes - genetics
Humans
Male
Middle Aged
Polymorphism, Restriction Fragment Length
Receptors, Estrogen - genetics
Russia
Sex Factors
Abstract
In order to identify genetic effects of allelic variation on bone mineral density (BMD), association studies have been performed recently. Examining the relation between PvuII and XbaI restriction fragment length polymorphism (RFLPs) at the estrogen receptor (ER alpha) gene and BMD, in women or men, have yielded conflicting results. We analyzed the association between this polymorphism and BMD Z score values of cancellous bone at the 3rd finger in 344 members of nuclear families of European population, Chuvasha, living in Russia. The population sample included 183 males, aged 18-84, and 161 females, aged 23-79. The analysis has been performed separately for both sexes and for both generations (parents and offspring). We used a novel direct haplotyping method, which determines simultaneously each of the PvuII and XbaI RFLPs and their relation to each other. The haplotypes were represented as the combination of both polymorphic sites on the same chromosome, by using P/p and X/x for PvuII and XbaI restriction sites, respectively. The subjects were classified into 3 groups of genotypes: A = PXPX (homozygote for the PX haplotype); B = PXPx, PXpx (the heterozygotes for the PX haplotype); C = PxPx, Pxpx, pxpx (genotypes that are lacking the PX haplotype). The PXPX genotype (A) was associated with higher BMD Z score values in comparison to the genotypes that are lacking the PX haplotype (C), in total males [0.618 vs. -0.133 (p = 0.004)] and for the "sons" generation [0.724 vs. -0.198 (p = 0.02)]. Similar tendency was observed for the "fathers" generation (0.539 vs. -0.085), though the difference did not approach statistical significance (p = 0.087). These findings were not found in the female samples, nor in the "mothers" or "daughters" generations. The question if there are differences in the mode of action of estrogen through its receptor on bone mass, between the genders or between the males' generations, have to be further investigated.
PubMed ID
11838047 View in PubMed
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A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study.

https://arctichealth.org/en/permalink/ahliterature186025
Source
J Bone Miner Res. 2003 Apr;18(4):723-9
Publication Type
Article
Date
Apr-2003
Author
Bo Abrahamsen
Jonna Skov Madsen
Charlotte Landbo Tofteng
Lis Stilgren
Else Marie Bladbjerg
Søren Risom Kristensen
Kim Brixen
Leif Mosekilde
Author Affiliation
Department of Endocrinology, Odense University Hospital, Odense, Denmark. B.abrahamsen@dadlnet.dk
Source
J Bone Miner Res. 2003 Apr;18(4):723-9
Date
Apr-2003
Language
English
Publication Type
Article
Keywords
Alleles
Bone Density - genetics - physiology
Denmark - epidemiology
Estrogen Replacement Therapy
Female
Fractures, Bone - enzymology - epidemiology - genetics
Gene Frequency
Genotype
Humans
Longitudinal Studies
Methylenetetrahydrofolate Reductase (NADPH2) - genetics - physiology
Middle Aged
Osteoporosis, Postmenopausal - enzymology - genetics - prevention & control
Polymorphism, Genetic
Proportional Hazards Models
Prospective Studies
Risk factors
Abstract
A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) has recently been associated with bone mineral density (BMD) in postmenopausal Japanese women. It is not known whether this effect is also present in European populations and whether it is caused by lower peak bone mass or accelerated postmenopausal bone loss. MTHFR genotyping was done in 1748 healthy postmenopausal Danish women participating in a prospective study of risk factors for osteoporosis. At the time of enrollment, 3-24 months after last menstrual period, the less prevalent genotype (TT, 8.7% of the population) was associated with significantly lower BMD at the femoral neck (ANOVA, p
PubMed ID
12674333 View in PubMed
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A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women.

https://arctichealth.org/en/permalink/ahliterature177097
Source
J Clin Endocrinol Metab. 2004 Dec;89(12):6173-8
Publication Type
Article
Date
Dec-2004
Author
E. Grundberg
T. Carling
H. Brändström
S. Huang
E L Ribom
O. Ljunggren
H. Mallmin
A. Kindmark
Author Affiliation
Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden. elin.grundberg@medsci.uu.se
Source
J Clin Endocrinol Metab. 2004 Dec;89(12):6173-8
Date
Dec-2004
Language
English
Publication Type
Article
Keywords
Adult
Bone Density - genetics
Cohort Studies
DNA-Binding Proteins - genetics
Estrogen Receptor alpha - metabolism
Female
Gene Deletion
Genotype
Histone-Lysine N-Methyltransferase
Humans
Nuclear Proteins - genetics
Polymorphism, Genetic
Random Allocation
Sweden
Transcription Factors - genetics
Abstract
Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture, and the trait is under genetic control by a large number of genes. It is recognized that estrogen plays an important role in the maintenance of bone mass by binding to estrogen receptor alpha (ERalpha). RIZ1 has previously been shown to be a specific ERalpha coactivator and strongly enhances its function both in vivo and in vitro. We performed in vitro studies comparing the abilities of RIZ1 P704 polymorphic variants (homozygous presence, P704+; absence, P704-; heterozygosity P704(+/-) of a proline at position 704) to coactivate the ERalpha and also examined the polymorphism associated to BMD of 343 Swedish women, aged 20-39 yr. The expression vector containing P704- RIZ1 showed an impaired response in coactivating ERalpha in a ligand- and dose-dependent manner compared with P704+ RIZ (P
PubMed ID
15579774 View in PubMed
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Determinants of peak bone mass: clinical and genetic analyses in a young female Canadian cohort.

https://arctichealth.org/en/permalink/ahliterature202198
Source
J Bone Miner Res. 1999 Apr;14(4):633-43
Publication Type
Article
Date
Apr-1999
Author
L A Rubin
G A Hawker
V D Peltekova
L J Fielding
R. Ridout
D E Cole
Author Affiliation
Division of Rheumatology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
Source
J Bone Miner Res. 1999 Apr;14(4):633-43
Date
Apr-1999
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Bone Density - genetics - physiology
Canada
Cohort Studies
Female
Genotype
Haplotypes
Hip
Humans
Multivariate Analysis
Osteoporosis - etiology - genetics - physiopathology
Receptors, Calcitriol - genetics
Risk factors
Spine
Abstract
Peak bone mass has been shown to be a significant predictor of risk for osteoporosis. Previous studies have demonstrated that skeletal mass accumulation is under strong genetic control, and efforts have been made to identify candidate loci. Determinants of peak bone mass also include diet, physical activity, hormonal status, and other clinical factors. The overall contribution of these factors, genetic and nongenetic, and their interaction in determining peak bone density status have not been delineated. Six hundred and seventy-seven healthy unrelated Caucasian women ages 18-35 years were assessed. A detailed, standardized interview was conducted to evaluate lifestyle factors, menstrual and reproductive history, medical conditions, medication use, and family history of osteoporosis. Bone mineral density (BMD) was measured at the lumbar spine (L2-L4) and the femoral neck (hip) using dual-energy X-ray absorptiometry. Genotyping of the vitamin D receptor (VDR) locus at three polymorphic sites (BsmI, ApaI, and TaqI) was performed. In bivariate analyses, BMD at the lumbar spine and hip was positively correlated with weight, height, body mass index (BMI), and level of physical activity, both now and during adolescence, but negatively correlated with a family history of osteoporosis. Hip, but not spine BMD, correlated positively with dietary intake of calcium, and negatively with amenorrhea of more than 3 months, with caffeine intake, and with age. Spine, but not hip BMD, correlated positively with age and with number of pregnancies. VDR haplotype demonstrated significant associations with BMD at the hip, level of physical activity currently, and BMI. In multivariate analysis, independent predictors of greater BMD (at the hip or spine) were: age (younger for the hip, older for the spine), greater body weight, greater height (hip only), higher level of physical activity now and during adolescence, no family history of osteoporosis, and VDR genotype (hip only). Weight, age, level of physical activity, and family history are independent predictors of peak BMD. Of these factors, weight accounts for over half the explained variability in BMD. VDR alleles are significant independent predictors of peak femoral neck, but not lumbar spine BMD, even after adjusting for family history of osteoporosis, weight, age, and exercise. However, the overall contribution of this genetic determinant is modest. Taken together, these factors explained approximately 17% and 21% of the variability in peak spine and hip BMD, respectively, in our cohort. Future research should be aimed at further evaluation of genetic determinants of BMD. Most importantly, understanding the critical interactive nature between genes and the environment will facilitate development of targeted strategies directed at modifying lifestyle factors as well as earlier intervention in the most susceptible individuals.
PubMed ID
10234586 View in PubMed
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Familial resemblance of bone mineral density between females 18 years and older and their mothers.

https://arctichealth.org/en/permalink/ahliterature192580
Source
Can J Public Health. 2001 Sep-Oct;92(5):353-8
Publication Type
Article
Author
D. Picard
A. Imbach
M. Couturier
R. Lepage
M. Picard
Author Affiliation
Department of Nuclear Medicine, Hôpital Saint-Luc and Université de Montréal, Montreal, QC.
Source
Can J Public Health. 2001 Sep-Oct;92(5):353-8
Language
English
Publication Type
Article
Keywords
Adult
Body Composition - genetics
Body Height - genetics
Body mass index
Body Weight - genetics
Bone Density - genetics
Canada
Female
Genetic Predisposition to Disease
Humans
Middle Aged
Mothers
Nutrition Assessment
Osteoporosis - genetics
Pedigree
Premenopause - physiology
Regression Analysis
Abstract
Potential determinants of bone mass were investigated in a group of 70 young females (mean age 26.6 years), daughters of women studied in premenopause. Nutritional data, leisure physical activity level, lifestyle habits as well as familial similarities were assessed. The daughters' bone mineral density (BMD), measured by dual-energy absorptiometry, was significantly correlated with their body mass index (BMI) (r = 0.22), dietary vitamin D intake (r = 0.19) and their mothers' BMD (r = 0.44). Multiple regression analysis indicated that only the mothers' BMD remained an independent predictor of bone mass. Mother-daughter correlations were also observed for body weight (r = 0.24), height (r = 0.39), BMI (r = 0.29), dietary calcium intake (r = 0.20), and calcium (r = 0.20) or vitamin D (r = 0.25) intakes from dairy products. Hence, these observations support the evidence that mothers' BMD is the strongest predictor of bone mass of young women in their third decade.
PubMed ID
11702488 View in PubMed
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FGF23 gene variation and its association with phosphate homeostasis and bone mineral density in Finnish children and adolescents.

https://arctichealth.org/en/permalink/ahliterature265785
Source
Bone. 2015 Feb;71:124-30
Publication Type
Article
Date
Feb-2015
Author
Minna Pekkinen
Christine M Laine
Riikka Mäkitie
Eira Leinonen
Christel Lamberg-Allardt
Heli Viljakainen
Outi Mäkitie
Source
Bone. 2015 Feb;71:124-30
Date
Feb-2015
Language
English
Publication Type
Article
Keywords
Absorptiometry, Photon
Adolescent
Bone Density - genetics
Bone and Bones - radiography
Child
Densitometry
Female
Fibroblast Growth Factors - chemistry - genetics
Finland
Genetic Association Studies
Genetic Variation
Haplotypes - genetics
Homeostasis
Humans
Linear Models
Male
Phosphates - metabolism
Polymorphism, Single Nucleotide - genetics
Protein Structure, Tertiary
Tomography, X-Ray Computed
Abstract
Fibroblast growth factor 23 (FGF23), a bone-derived hormone, participates in the hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25-dihydroxyvitamin D, plasma phosphate (Pi), and diet. Inappropriately high serum FGF23, seen in certain genetic and acquired disorders, results in urinary phosphate wasting and impaired bone mineralization. This study investigated the impact of FGF23 gene variation on phosphate homeostasis and bone health. The study included 183 children and adolescents (110 girls) aged 7-19 years (median 13.2years). Urine and blood parameters of calcium and phosphate homeostasis were analyzed. Bone characteristics were quantified by DXA and peripheral quantitative computed tomography (pQCT). Genetic FGF23 variation was assessed by direct sequencing of coding exons and flanking intronic regions. Nine FGF23 polymorphisms were detected; three of them were common: rs3832879 (c.212-37insC), rs7955866 (c.716C>T, p.T239M) and rs11063112 (c.2185A>T). Four different haplotypes and six different diplotypes were observed among these three polymorphisms. The variations in FGF23 significantly associated with plasma PTH and urinary Pi excretion, even after adjusting for relevant covariates. FGF23 variations independently associated with total hip BMD Z-score, but not with other bone outcomes. In instrument analysis, genetic variance in FGF23 was considered a weak instrument as it only induced small variations in circulating FGF23, PTH and Pi concentrations (F statistic less than 10). The observed associations between FGF23 variations and circulating PTH, and Pi excretion and total hip BMD Z-scores suggest that FGF23 polymorphisms may play a role in mineral homeostasis and bone metabolism.
PubMed ID
25445451 View in PubMed
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35 records – page 1 of 4.