Is there any association between osteoporotic vertebral fracture and vitamin K epoxide reductase complex subunit-1 polymorphism in Turkish society? A pilot study

OBJECTIVE: In this study, the relationship between osteoporotic vertebral fractures and 9041 Guanine/Adenine and 3673 Guanine/Adenine polymorphisms related to the vitamin K epoxide reductase complex subunit-1 (VKORC1) gene in postmenopausal women with osteoporosis was investigated. METHOD: DNA was isolated from blood samples collected from 150 women with postmenopausal osteoporosis. Genotyping of the two polymorphic regions (9041 Guanine/Adenine and 3673 Guanine/Adenine) in VKORC1 was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. The presence of radiographic fractures among the 150 patients was ascertained by using the Genant method. RESULT: At least one fracture was detected in 98 patients, and no fracture was observed in 52 patients on radiological images. We found no association between the 9041 Guanine/Adenine (p=0.283) and 3673 Guanine/Adenine (p=0.232) polymorphisms of the VKORC1 gene and the development of secondary postosteoporotic fractures in our study. CONCLUSION: There was no relationship between osteoporotic vertebral fracture and VKORC1 gene polymorphism in a postmenopausal Turkish population.

Frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low bone mineral density / Frequência do polimorfismo da interleucina-6, GST, e dos receptores de progesterona em mulheres na pós-menopausa com baixa densidade mineral óssea

CONTEXT AND OBJECTIVE: Osteoporosis is a skeletal disorder characterized by low bone mineral density (BMD). Studies have shown that some of the genetic components relating to lower BMD may be detected by polymorphisms. Our aim was to evaluate the frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low BMD. DESIGN AND SETTING: Cross-sectional study, conducted in a public university in São Paulo, Brazil. METHODS : We evaluated interleukin-6 (IL-6), progesterone receptor gene (PROGINS) and glutathione S-transferase (GST) polymorphisms in 110 postmenopausal women with no previous use of hormone therapy. Tests were performed using DNA-PCR, from oral scrapings. We used Student's t-test and a logistic regression model for statistical analysis. RESULTS : Regarding IL-6 polymorphism, 58.2% of the patients were homozygotes (GG) and 41.8% had allele C (heterozygote or mutant homozygote + GC or CC). PROGINS genotype polymorphism was absent in 79% (wild homozygote or P1/P1) and present in 20.9% (heterozygote or P1/P2). Regarding GSTM1 polymorphism, the allele (1/1) was present in 72.7% of the patients and was absent in 27.3%. We found that IL-6 polymorphism had statistically significant correlations with the L2-L4 T-score (P = 0.032) and with BMD (P = 0.005). Women with IL-6 polymorphism were 2.3 times more likely to have a L2-L4 T-score of less than -1, compared with those not presenting this polymorphism. CONCLUSION: IL-6 gene polymorphism was correlated with low BMD, whereas the PROGINS and GSTM1 polymorphisms did not show any correlation. .

CONTEXTO E OBJETIVO: A osteoporose é uma desordem esquelética caracterizada por baixa densidade mineral óssea. Estudos têm demonstrado que alguns componentes genéticos relacionados com a menor densidade mineral óssea podem ser detectados por polimorfismos. Nosso objetivo foi avaliar a presença do polimorfismo de genes em mulheres pós-menopáusicas com baixa densidade mineral óssea. TIPO DE ESTUDO E LOCAL: Estudo transversal, conduzido em universidade pública em São Paulo, Brasil. MÉTODOS: Avaliamos os polimorfismos relacionados à interleucina-6 (IL-6), o gene receptor de progesterona (PROGINS) e glutationa S-transferase (GST) em 110 mulheres na pós-menopausa sem terapia hormonal prévia. Os testes foram realizados com DNA-PCR a partir de raspados orais. Foram utilizados teste t de Student e modelo de regressão logística para análise estatística. RESULTADOS: Em relação ao polimorfismo IL-6, 58,2% dos pacientes eram homozigotos (GG) e 41,8% tinham o alelo C (heterozigoto ou homozigoto mutante + GC ou CC). Nos genótipos do polimorfismo PROGINS, 79% estavam ausentes (homozigoto selvagem ou P1/P1) e 20,9% presentes (heterozigoto ou P1/P2). No polimorfismo do GSTM1, o alelo (1/1) estava presente em 72,7% dos pacientes e ausente em 27,3%. Encontramos significância estatística entre o polimorfismo genético da IL-6 com o T-score de L2-L4 (P = 0,032) e a densidade mineral óssea (P = 0,005). As mulheres com polimorfismo da IL-6 tiveram 2,3 vezes mais chance de ter menos de -1 na L2-L4 T-score, quando comparadas às não portadoras. CONCLUSÃO: O polimorfismo do gene da IL-6 está correlacionado com baixa densidade mineral óssea, enquanto os polimorfismos GSTM1 e PROGINS não mostraram correlação. .

Relationship between plasminogen activator inhibitor type-1 (PAI-1) gene polymorphisms and osteoporosis in Turkish women

OBJECTIVE: The development of osteoporosis is associated with several risk factors, such as genetic structures that affect bone turnover and bone mass. The impact of genetic structures on osteoporosis is not known. Plasminogen activator inhibitor type-1 regulates the bone matrix and bone balance. This study assessed the correlation between plasminogen activator inhibitor type-1 gene 4G/5G polymorphisms and osteoporosis in a population of Turkish women. METHODS: A total of 195 postmenopausal female patients who were diagnosed with osteoporosis (Group I) based on bone mineral density measurements via dual-energy x-ray absorptiometry and 90 females with no osteoporosis (Group II) were included in this study. Correlations between PAI-1 gene 4G/5G polymorphisms and osteoporosis were investigated through the identification of PAI-1 gene 4G/5G polymorphism genotypes using the polymerase chain reaction. RESULTS: No significant differences in the genotype and allele frequency of 4G/5G plasminogen activator inhibitor type-1 polymorphisms were observed between the two groups, and both groups exhibited the most frequently observed 4G5G genotype. CONCLUSION: No correlation between the development of osteoporosis in the female Turkish population and 4G/5G plasminogen activator inhibitor type-1 gene polymorphisms was observed.

Association of ADIPOR1 polymorphisms with bone mineral density in postmenopausal Korean women

Adiponectin may affect bone through interactions with two known receptors, adiponectin receptors (ADIPOR) 1 and 2. We examined the association between polymorphisms of ADIPOR1 and ADIPOR2 and bone mineral density (BMD) in postmenopausal Korean women. Six polymorphisms in ADIPOR1 and four polymorphisms in ADIPOR2 were selected and genotyped in all study participants (n = 1,329). BMD at the lumbar spine and femur neck were measured using dual-energy X-ray absorptiometry. Lateral thoracolumbar (T4-L4) radiographs were obtained for vertebral fracture assessment and the occurrence of non-vertebral fractures examined using self-reported data. P values were adjusted for multiple testing using Bonferroni correction (Pcorr). ADIPOR1 rs16850799 and rs34010966 polymorphisms were significantly associated with femur neck BMD (Pcorr = 0.036 in the dominant model; Pcorr = 0.024 and Pcorr = 0.006 in the additive and dominant models, respectively). Subjects with the rare allele of each polymorphism had lower BMD, and association of rs34010966 with BMD showed a gene dosage effect. However, ADIPOR2 single nucleotide polymorphisms and haplotypes were not associated with BMD at any site. Our results suggest that ADIPOR1 polymorphisms present a useful genetic marker for BMD in postmenopausal Korean women.

Polimorfismos del gen del receptor de vitamina D y riesgo de fractura de cadera en la mujer adulta mayor de la Región del Bío Bío / Vitamin D receptor gene polymorphisms and risk of hip fracture in Chilean elderly women

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.

Analysis of polymorphism of the interleukin-6 gene in Thai subjects with osteoporosis.

Osteoporosis is the imbalance between bone formation by osteoblast and bone resorption by osteoclast. The genetic factors play an important role in determining bone mass and several genes probably act as regulators of this process. Interkeukin-6 (IL-6) is one of the candidate genes to regulate bone density, since IL-6 has some effect on stimulation of osteoclast resorption and has been implicated in the pathogenesis of bone loss associated with estrogen deficiency. We investigated the relationship between bone mineral density (BMD) and a polymorphic AT rich repeat in the 3' flank of the IL-6 gene in 272 Thai subjects. The subjects were classified into 3 groups i.e. normal healthy control (n=95), border-line (n=112) and osteoporotic patients (n=65). Five alleles different in sizes were identified (designated a, b, c, e and f). It was observed that c/c was the most common genotype in Thais (86.76%). The other genotype frequencies were 0.74, 3.31, 8.09, 0.74 and 0.37 for a/c, b/c, c/e, c/f and b/e genotypes, respectively. The common genotype was different from the Caucasians in a previous study. These frequencies were significantly different from the Caucasians (p<0.05). There was no significant relationship between 3' flanking AT repeat of the IL-6 genotypes and the BMD values of the distal forearm that were determined by One-way ANOVA (p>0.05). Additionally, the impact of the IL-6 genotypes on risk of osteoporosis was assessed by determination of the odds ratio. The c/e genotype may be a protective factor of osteoporosis. On the contrary, the b/c and c/c genotypes were considered to be risk factors of osteoporosis.

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 + 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 + 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 + 6.6 years (mean+SD). Analysis of VDR gene polymorphism by restriction fragment lenght polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5 percent BB, 42.5 percent and 37 percent bb did not differ significantly from the values obtained for group II (16 percent BB, 36 percent Bb and 48 percent bb) or for group III (10.2 percent BB, 47.6 percent Bb and 41.8 percent bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurence of osteoporotic fractures with advancing age.

Fisiopatologia da osteoporose pós-menopausa / Osteoporosis in post menopause physiopathology

A osteoporose pós menopáusica se caracteriza por um aumento da remodelaçao óssea, havendo predomínio da reabsorçao sobre a formaçao óssea, com balanço de cálcio negativo e perda progressiva de massa óssea. O hipoestrogenismo pós menopáusico é responsável por esse processo, havendo por outro lado, conservaçao da massa óssea em pacientes sob terapêutica de reposiçao hormonal. Os mecanismos pelos quais os estrogênios atuam na conservaçao da massa óssea sao revisados neste artigo, à luz dos conhecimentos atuais. O metabolismo local do tecido ósseo é enfocado, referindo-se o papel das citocinas no controle da freqüência de ativaçao das unidades de remodelaçao óssea e suas inter-relaçoes com os níveis plasmáticos e tissulares de estrogênios.