RESUMO
AIMS: Osteoporosis (OP) remains a major public health problem worldwide. The most serious complications of this disease are fragility fractures, which increase morbidity and mortality. Management of OP represents an economic burden for health systems. Therefore, it is necessary to develop new screening strategies to identify the population at risk and implement preventive measures. We previously identified the SNPs rs3801387 in WNT16, rs7108738 in SOX6, rs10036727 in SLIT3 and rs7584262 in PKDCC as associated with bone mineral density in postmenopausal women through a genome-wide association study. The aim of this study was to validate those SNPs in two independent cohorts of non-related postmenopausal women. MATERIALS AND METHODS: We included 1160 women classifying them as normal, osteopenic or osteoporotic and a group with hip fragility fracture. Genotyping was performed using predesigned TaqMan assays. RESULTS: The variants rs10036727 and rs7108738 showed a significant association with BMD at the femoral neck. SLIT3 has been previously proposed as a potential biomarker and therapeutic resource. CONCLUSIONS: Our results provide new evidence regarding a possible involvement of SLIT3 in bone metabolisms and encourage the development of more studies in different populations to support these observations.
Assuntos
Densidade Óssea/genética , Proteínas de Membrana/genética , Osteoporose Pós-Menopausa/genética , Fatores de Transcrição SOXD/genética , Absorciometria de Fóton , Idoso , Doenças Ósseas Metabólicas/genética , Feminino , Colo do Fêmur/diagnóstico por imagem , Fraturas do Quadril/genética , Humanos , Vértebras Lombares/diagnóstico por imagem , México , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico por imagem , Fraturas por Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa , Proteínas Tirosina Quinases/genética , Proteínas Wnt/genéticaRESUMO
OBJECTIVE: This study aimed to investigate the association of seven single nucleotide polymorphisms (SNPs) on the RMND1, CCDC170, and ESR1 genes with osteoporosis or hip fracture in a postmenopausal Mexican population. METHODS: We included a group of 400 postmenopausal women from the Health Workers Cohort Study from the Mexican Institute of Social Security. As a replication sample, we recruited 423 postmenopausal women from the National Institute of Rehabilitation. Demographic data were collected through a structured questionnaire. Bone mineral density was assessed using dual X-ray absorptiometry. Individuals were classified as normal, osteopenia, osteoporosis, and fracture, according to World Health Organization criteria. Genotyping was performed using predesigned TaqMan Probes. Linear regression analysis was used to investigate association. RESULTS: All of the analyzed SNPs showed association with at least one of the phenotypes of the study groups. In addition, we observed a region with linkage disequilibrium within the ESR1 gene in all groups. CONCLUSION: This study shows that an association of the SNPs can exist with osteopenia, osteoporosis, or fragility fracture. Our results agree with data published elsewhere, supporting the potential of these loci for the identification of the population at risk. However, additional studies are required to determine the extent of this association for other geographic regions of Mexico.
Assuntos
Densidade Óssea/genética , Fraturas do Quadril/genética , Osteoporose Pós-Menopausa/genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa , Absorciometria de Fóton , Idoso , Proteínas de Transporte/genética , Proteínas de Ciclo Celular/genética , Estudos de Coortes , Receptor alfa de Estrogênio/genética , Feminino , Frequência do Gene , Haplótipos , Humanos , Modelos Lineares , Desequilíbrio de Ligação , México , Pessoa de Meia-Idade , Ossos Pélvicos/patologiaRESUMO
The RANK/RANKL/OPG signaling is important in the regulation of bone turnover. The aim of the present work was to analyze the rs3018362 and rs12585014 polymorphisms in the RANK and RANKL genes, as well as risk factors in postmenopausal women. Women with hip fracture, with femoral neck osteoporosis and controls (n = 646) were recruited. From these, 303 women who fulfill the inclusion criteria were genotyped using real-time PCR with TaqMan probes. There were no associations of the rs3018362 and rs12585014 with osteoporosis or fracture. When women were divided by age at menarche, the rs12585014 GG genotype was strongly associated with age at menarche >13 years [p = .00774, OR = 6.429 (1.907-21.103)] in women with hip fracture. Significant differences in risk factors such as body mass index, age at menopause, use of estrogens, the presence of hypertension, and diabetes mellitus were found. Carrying the GG genotype of rs12585014 entails a higher risk of having menarche later (>13 years), which could involves a greater risk of fractures. The rs3018362 and rs12585014 do not seem to be associated with hip osteoporosis or hip fracture in Mexican women.
Assuntos
Fraturas do Quadril/genética , Menarca/genética , Osteoporose Pós-Menopausa/genética , Ligante RANK/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , HumanosRESUMO
BACKGROUND AND AIMS: Polymorphisms in Interleukin-6 (IL6) and its receptor (IL6R) have been associated with bone mineral density. In this work, the G-174C and G-572C polymorphisms in IL6, G-208A, and Asp358Ala in IL6R were analyzed in Mexican women with hip fracture. METHODS: Postmenopausal Mexican women (60 years or over) with hip fragility fracture (77.97 ± 8 years) and without hip fracture (70.5 ± 7.02 years) were genotyped by real-time PCR. RESULTS: The rs1800796 GG genotype was associated with low risk of fracture (p = 0.05), while GC genotype was associated with high risk of fracture [p = 0.047, OR 2.3 (95% CI 1.013-5.2)]. The AA genotype of the rs2228145 SNP (IL6R) was significantly different [p = 0.033, OR 1.94 (95% CI 1.01-3.75)], but when data were adjusted by age and body mass index, there were no differences (p = 0.9). CONCLUSION: Our results suggest that the IL6 rs1800796 SNP is a good marker for hip fracture risk in Mexican women.
Assuntos
Fraturas do Quadril/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-6/genética , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Densidade Óssea , Feminino , Genótipo , Fraturas do Quadril/etiologia , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIMS: Osteoporosis leads to high fracture risk and evidence suggests that genetic factors play an important role in this disease. The aim was to evaluate the association of two polymorphisms (-1997G/T, +1245G/T) in the collagen type1 alpha 1 gene (COL1A1) with fracture or with low bone mineral density (BMD) at the hip in postmenopausal Mexican women. METHODS: BMD was determined by bone densitometry and the risk factors were collected with a questionnaire. Genotyping was performed by real-time PCR. RESULTS: The polymorphisms were in Hardy-Weinberg equilibrium. The -1997G/+1245T haplotype showed, after adjustment for confounders, a fourfold increased risk of hip fracture [OR 4.32; p = 0.041 (95 % CI 1.07-17.43)]; while in the women with low BMD at the hip, the risk was increased threefold [OR 3.36; p = 0.022 (95 % CI 1.20-9.40)]. CONCLUSIONS: The results support the association of COL1A1 gene polymorphisms with fracture and with low BMD at the hip in Mexican population.
Assuntos
Densidade Óssea , Colágeno Tipo I/genética , Fraturas do Quadril/genética , Polimorfismo Genético , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/genética , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Genótipo , Haplótipos , Humanos , México , Pessoa de Meia-Idade , Osteoporose/genética , Pós-MenopausaRESUMO
A (TTTA)n polymorphism in the aromatase gene has been studied in relation to bone mineral density (BMD). The low number of TTTA repeats has been associated with low BMD and fracture risk. The aim of this study was to search for associations of TTTA copy number with hip fracture and lumbar spine osteoporosis in Mexican peri and postmenopausal women. The allele with seven repeats was present in the two reported versions, with or without a TCT deletion upstream of the microsatellite (A1 and A2, respectively). After adjustment by confounders, the A1 allele and the A1A1 genotype were significantly associated with an elevated risk of fracture (p = 0.034, OR = 3.2 [95% CI, 1.09-9.41] and p = 0.019, OR = 2.26 [95% CI, 1.14-4.49], respectively) and the A2 allele was associated with protection of hip fracture (p = 0.04, OR = 0.48, [95% CI, 0.22-1.05]) as the A2A2 genotype (p = 0.048, OR = 0.29 [95% CI, 0.06-1.16]). The analysis allowed us to defining the usefulness of the (TTTA)n polymorphism in the aromatase gene as an indicator of hip fracture risk in Mexican population.
Assuntos
Aromatase/genética , Predisposição Genética para Doença , Fraturas do Quadril/genética , Repetições de Microssatélites/genética , Polimorfismo Genético , Pós-Menopausa , Idoso , Alelos , Feminino , Genótipo , Humanos , Vértebras Lombares , México , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/genéticaRESUMO
Osteoporosis is a heritable disease characterized mainly by low bone mineral density (BMD) and/or osteoporotic fractures (OF). Most genome-wide association studies on osteoporosis have focused on BMD, whereas little effort has been expended to identify genetic variants directly linked to OF. To determine whether BMD-loci are also associated with OF risk, we performed a validation study to examine 23 BMD-loci reported by recent genome-wide association studies for association with hip OF risk. Our sample consisted of 700 elderly Chinese Han subjects, 350 with hip OF and 350 healthy matched controls. We identified four BMD-loci that were significantly associated with hip OF in this Chinese population, including 7q21 (FLJ42280, P = 1.17 × 10(-4) for rs4729260; P = 0.008 for rs7781370), 6p21 (MHC, P = 0.004 for rs3130340), 13q14 (TNFSF11, P = 0.012 for rs9533090; P = 0.018 for rs9594759; P = 0.020 for rs9594738; P = 0.044 for rs9594751), and 18q21 (TNFRSF11A, P = 0.015 for rs884205). The SNP rs4729260 at 7q21 remained significantly associated, even after conservative Bonferroni's correction. Our results further highlight the importance of these loci in the pathogenesis of osteoporosis, and demonstrate that it is feasible and useful to use OF as the direct phenotype to conduct genetic studies, to enhance our understanding of the genetic architecture of osteoporosis.
Assuntos
Densidade Óssea/genética , Fraturas do Quadril/genética , Osteoporose/genética , Fraturas por Osteoporose/genética , Idoso , Povo Asiático/genética , China/epidemiologia , Cromossomos/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Quadril/patologia , Articulação do Quadril/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/patologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: We aimed to discuss the risk assessments for both patients with hip fractures due to fall-related, low energy traumas and non-fractured control patients by examining bone mineral density and genetic data, two features associated with femoral strength and hip fracture risk. METHODS: Twenty-one osteoporotic patients with proximal femur fractures and non-fractured, osteoporotic, age- and gender-matched controls were included in the study. Bone mineral density measurements were performed with a Lunar DXA. The COL1A1, ESR, VDR, IL-6, and OPG genes were amplified, and labeling of specific gene sequences was performed in a multiplex polymerase chain reaction using the osteo/check PCR kit from the whole blood of all subjects. RESULTS: The bone mineral density (trochanteric and total bone mineral density values) of the fracture group was significantly decreased relative to the control group. We were not able to conduct statistical tests for the polymorphisms of the COL1A1, ESR, and VDR genes because our results were expressed in terms of frequency. Although they were not significant, we did examine differences in the IL-6 and OPG genes polymorphisms between the two groups. We concluded that increasing the number of cases will allow us to evaluate racial differences in femoral hip fracture risk by genotypes.
Assuntos
Densidade Óssea/genética , Colágeno Tipo I/genética , Receptor alfa de Estrogênio/genética , Fraturas do Quadril/genética , Interleucina-6/genética , Osteoprotegerina/genética , Absorciometria de Fóton/métodos , Acidentes por Quedas , Idoso , Estudos de Casos e Controles , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Predisposição Genética para Doença , Genótipo , Fraturas do Quadril/diagnóstico por imagem , Humanos , Masculino , Osteoporose/complicações , Osteoporose/diagnóstico por imagem , Osteoporose/genética , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Medição de Risco , TurquiaRESUMO
BACKGROUND: Osteoporotic hip fractures are devastating events in older women. There is a genetic modulation of bone phenotypic parameters including bone density (BMD) and bone fragility fractures. Vitamin D receptor (VDR) gene polymorphisms explain a small part of the genetic influence on BMD, whereas their effect on fractures remains uncertain. AIM: To examine the contributions of VDR genotypes to the susceptibility to hip fracture in elderly Chilean women. PATIENTS AND METHODS: We recruited 126 women (67 with fractures and 59 without) from Bio-Bio Region, Chile, aged 65 to 94 years. Genotyping for Bsm-l, Apa-1, Taq-1 and Fok-1 VDR polymorphisms was performed using polymerase chain reaction methods. All hip fractures were confirmed by X-ray. RESULTS: The allele frequencies were 0.49 for B, 0.57 for A, 0.60 for T and 0.65 for F in the Bsm-l, Apa-1, Taq-1 and Fok-1 polymorphisms respectively. The prevalence of these VDR gene polymorphisms in women with fractures were 16% BB, 69% Bb, 15% bb for Bsm-l; 30% AA, 46% Aa, 14% aa for Apa-1; 17% TT, 34 Tt, 8% tt for Taq-1 and 43%FF, 41% Ff, 16% ff for Fok-1. All VDR genotype frequencies did not differ from Hardy-Weinberg expectations. Allele or genotype frequencies did not differ between women with or without fractures. These results did not change when analysis was adjusted by age weight, height or gynecologic history. CONCLUSIONS: The genotype frequencies of the VDR polymorphisms are in accordance with the frequencies of other Hispanic and Caucasian populations. Our results suggest that VDR polymorphisms are not associated with the risk of hip fracture in older women of this Region of Southern Chile.
Assuntos
Predisposição Genética para Doença/genética , Fraturas do Quadril/genética , Osteoporose Pós-Menopausa/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/genética , Estudos de Casos e Controles , Chile , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
Background: Osteoporotic hip fractures are devastating events in older women. There is a genetic modulation of bone phenotypic parameters including bone density (BMD) and bone fragility fractures. Vitamin D receptor (VDR) gene polymorphisms explain a small part of the genetic influence on BMD, whereas their effect on fractures remains uncertain. Aim: To examine the contributions of VDR genotypes to the susceptibility to hip fracture in elderly Chilean women. Patients and methods: We recruited 126 women (67 with fractures and 59 without) from Bio-Bio Region, Chile, aged 65 to 94 years. Genotyping for Bsm-l, Apa-1, Taq-1 and Fok-1 VDR polymorphisms was performed using polymerase chain reaction methods. All hip fractures were confirmed by X-ray. Results: The alíele frequencies were 0.49 for B, 0.57 for A, 0.60 for T and 0.65 for F in the Bsm-l, Apa-1, Taq-1 and Fok-1 polymorphisms respectively. The prevalence of these VDR gene polymorphisms in women with fractures were 16 percent BB, 69 percent Bb, 15 percent bb for Bsm-l; 30 percent AA, 46 percent Aa, 14 percent aa for Apa-1; 17 percent TT, 34 Tt, 8 percent tt for Taq-1 and 43 percentFF, 41 percent Ff, 16 percent ff for Fok-1. All VDR genotype frequencies did not differ from Hardy- Weinberg expectations. Alíele or genotype frequencies did not differ between women with or without fractures. These results did not change when analysis was adjusted by age weight, height or gynecologic history. Conclusions: The genotype frequencies of the VDR polymorphisms are in accordance with the frequencies of other Hispanic and Caucasian populations. Our results suggest that VDR polymorphisms are not associated with the risk of hip fracture in older women of this Region of Southern Chile.