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Biomedical subjects

Satoshi Inoue

Publications and source records attributed to Satoshi Inoue.

At least 109 records · Page 6Linked to original sources
PubMed2003

Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR.

Vitamin K2 is a critical nutrient required for blood clotting that also plays an important role in bone formation. Vitamin K2 supplementation up-regulates the expression of bone markers, increases bone density in vivo, and is used clinically in the management of osteoporosis. The mechanism of vitamin K2 action in bone formation was thought to involve its normal role as an essential cofactor for gamma-carboxylation of bone matrix proteins. However, there is evidence that suggests vitamin K2 also has a transcriptional regulatory function. Vitamin K2 bound to and activated the orphan nuclear receptor SXR and induced expression of the SXR target gene, CYP3A4, identifying it as a bona fide SXR ligand. Vitamin K2 treatment of osteosarcoma cells increased mRNA levels for the osteoblast markers bone alkaline phosphatase, osteoprotegerin, osteopontin, and matrix Gla protein. The known SXR activators rifampicin and hyperforin induced this panel of bone markers to an extent similar to vitamin K2. Vitamin K2 was able to induce bone markers in primary osteocytes isolated from wild-type murine calvaria but not in cells isolated from mice deficient in the SXR ortholog PXR. We infer that vitamin K2 is a transcriptional regulator of bone-specific genes that acts through SXR to favor the expression of osteoblastic markers. Thus, SXR has a novel role as a mediator of bone homeostasis in addition to its role as a xenobiotic sensor. An important implication of this work is that a subset of SXR activators may function as effective therapeutic agents for the management of osteoporosis.

Alkaline Phosphatase↗
PubMed2003

Association of genetic variation of the RIL gene, encoding a PDZ-LIM domain protein and localized in 5q31.1, with low bone mineral density in adult Japanese women.

Twin and family studies had shown that genetic factors are important determinants of bone mass. Multiple genes might be involved. One candidate gene, the reversion-induced LIM gene ( RIL), is a PDZ and LIM-domain-containing protein and has been localized within the cytokine cluster of chromosome 5 (5q31.1). In a genetic study of 370 adult Japanese women, we investigated the correlation between radial bone mineral density (BMD) and a genetic variation (-3333T-->C) of the 5'-flanking region of RIL gene. A significant association was identified between the RIL variation -3333T-->C and radial BMD ( r=0.15, P=0.003). The variation of the RIL locus may be an important determinant of osteoporosis.

Adult↗
PubMed2003

Association of the -381T/C promoter variation of the brain natriuretic peptide gene with low bone-mineral density and rapid postmenopausal bone loss.

Osteoporosis is believed to result from interplay among multiple environmental and genetic determinants, including factors that regulate bone-mineral density (BMD). Recent quantitative trait locus analysis in human suggested a possible involvement of chromosomal region 1p36.2-p36.3 for determination of BMD. The brain natriuretic peptide (BNP, also named NPPB) gene lies within this candidate region for BMD determination. Overexpression of the BNP resulted in skeletal overgrowth in transgenic mice. Association analysis between nucleotide variations of the BNP gene and radial BMD in 378 Japanese postmenopausal women revealed a significant association of the -381T/C variation of the BNP gene with radial BMD (r = 0.17, P = 0.01). Homozygous T-allele carriers had the lowest BMD values (0.395 +/- 0.056 g/cm(2)), homozygous C-allele carriers had the highest (0.429 +/- 0.051 g/cm(2)), and heterozygous individuals had intermediate radial BMD values (0.405 +/- 0.048 g/cm(2)), indicating a dosage effect. Accelerated bone loss also correlated with the -381 T allele in a 5-year follow-up study (r = 0.21, P = 0.017). These results suggest that variation of BNP may be an important determinant of postmenopausal osteoporosis, in part through the mechanism of accelerated postmenopausal bone loss.

Adult↗
PubMed2003

Correlation of the dose of midazolam for symptom control with administration periods: the possibility of tolerance.

Although tolerance to midazolam is sometimes described in the palliative care literature, no studies have systemically examined the possibility. To explore the association between midazolam dose for symptom palliation and the administration period, a retrospective study was performed on 62 terminally ill cancer patients who required parenteral midazolam in the final three days of life. The mean maximum dose and administration period of midazolam were 38 +/- 45 mg/day (median = 24) and 10 +/- 19 days (median = 2.5), respectively. Thirteen patients (21%) received midazolam at a dose of 60 mg/day or more, and 13 patients (21%) received it for 14 days or longer. The maximum doses were significantly correlated with patient age (rho = -0.32, P = 0.012) and the administration period (rho = 0.47, P < 0.01); and were significantly higher in patients who received midazolam for 14 days or longer (74 +/- 63 mg/day vs. 28 +/- 34 mg/day, P < 0.01). Multivariate analyses revealed that younger age (< or =70) and longer administration periods (> or =14 days) were independent determinants for a midazolam requirement of 60 mg/day or more (odds ratios [95% C.I.] = 0.091 [0.009 - 0.92], P = 0.042; 11 [2.3 - 54], P < 0.01; respectively). The significant correlation of midazolam doses with administration period suggests that the longer use of midazolam can result in the development of tolerance. This finding suggests that midazolam should be reserved for patients with limited prognoses.

Adjuvants, Anesthesia↗
PubMed2003

Impaired communication capacity and agitated delirium in the final week of terminally ill cancer patients: prevalence and identification of research focus.

The maintenance of intellectual activity is an important area in the "good death" concept. To clarify the communication capacity levels of terminally ill cancer patients in their final week, and to identify factors contributing to the development of communication capacity impairment and agitated delirium, a retrospective study was performed on 284 consecutive hospice inpatients. The data were collected by chart review, and two independent raters measured the degree of communication capacity and agitation in the last week, using multiple items from the Memorial Delirium Assessment Scale, the Communication Capacity Scale, and the Agitation Distress Scale. The percentages of patients who could achieve complex communication were 43%, 28%, and 13% at 5 days, 3 days, and 1 day before death, respectively. Agitated delirium was identified in 20%. Patients receiving opioids at a dose of > or =120 mg oral morphine equivalents/day one week before death were significantly unable to communicate clearly 3 days before death (0.48 [0.28-0.84], P=0.011). Male gender and the presence of icterus were identified as significant contributors to the development of agitated delirium (odds ratios [95% C.I.]=2.6 [1.4-5.0], P<0.01; 2.4 [1.3-4.4], P< 0.01). These findings demonstrate that communication capacity impairment and agitated delirium are frequently observed in terminally ill cancer patients, and are significantly correlated with a higher dose requirement of opioids and the presence of icterus. To explore the best management to maintain the intellectual activity of dying patients, research should focus on a homogeneous sample of patients receiving high-dose opioids and those with hepatic encephalopathy. In the meanwhile, clinicians should educate patients and family members about the nature of the dying process and help facilitate the completion of life purposes requiring complex mental activities before the latest stages of cancer.

Aged↗
PubMed2003

Estrogen-responsive RING finger protein controls breast cancer growth.

Most of the breast cancers initially respond to endocrine therapy that reduces the levels of estrogens or competes with estrogen for binding to its receptor. Most of the patients, however, acquire resistance to endocrine therapy with tamoxifen and aromatase inhibitors later. We assumed that identification of estrogen-responsive genes those regulate the growth of breast cancer is indispensable to develop new strategies targeting the genes and overcome the resistance to current endocrine therapy. Estrogen-responsive finger protein (Efp) is one of the estrogen receptor (ER)-target genes we have cloned using genomic binding site cloning. Efp features a structure of the RING-finger B-box coiled-coil (RBCC) motif. We postulated that Efp is a critical factor in proliferation of breast tumors. In a model system using MCF7 cells grown in xenografts, we showed that inhibition of Efp expression by antisense oligonucleotide reduced the tumor growth. MCF7 cells overexpressing Efp formed tumors in xenografts even in estrogen deprivation environment. By yeast two-hybrid screen, we identified that Efp interacts with 14-3-3sigma, which is known as a cell cycle brake that causes G2 arrest and expressed in normal mammary glands. In vitro studies have revealed that Efp functions as a ubiquitin-protein ligase (E3) that targets 14-3-3sigma. These data suggest that Efp controls breast cancer growth through ubiquitin-dependent proteolysis of 14-3-3sigma. Future studies may provide a new therapy to block breast tumor proliferation by targeting Efp.

14-3-3 Proteins↗
PubMed2003

Association of a Trp16Ser variation in the gonadotropin releasing hormone signal peptide with bone mineral density, revealed by SNP-dependent PCR typing.

Osteoporosis is believed to result from interplay among multiple environmental and genetic determinants, including factors that regulate bone mineral density (BMD). Among those factors, adequate estrogen is essential for achievement of peak bone mass as well as for postmenopausal maintenance of skeletal homeostasis. Gonadotropin-releasing hormone (GnRH) from the hypothalamus is the primary determinant in the hypothalamic-pituitary-gonadal feedback system. In genetic studies of 384 postmenopausal Japanese women, we found a significant association between BMD and an amino acid variation (Trp16Ser) located within the signal peptide of GnRH (r = 0.143, P = 0.005). These results were achieved by genotyping all subjects using a newly developed SNP-dependent PCR method. This automated, high-throughput, and inexpensive procedure is suitable for typing large numbers of samples. BMD was lowest among 16Ser/Ser homozygotes, highest among 16Trp/Trp homozygotes, and intermediate among heterozygotes. A case-control study involving 125 osteoporosis patients and 92 healthy controls revealed a significant association between the presence of a 16Ser GnRH allele and affected status (chi(2) = 4.74, P = 0.041). The results suggested that variation of the GnRH signal peptide may be an important risk factor for postmenopausal osteoporosis.

Adult↗
PubMed2003

Association of a promoter haplotype (-1542G/-525C) in the tumor necrosis factor receptor associated factor-interacting protein gene with low bone mineral density in Japanese women.

Osteoporosis, a multifactorial common disease, is believed to result from the interplay of multiple environmental and genetic factors that regulate bone mineral density (BMD). Tumor necrosis factor receptor associated factor-interacting protein (I-TRAF) is an essential effecter of the tumor necrosis factor receptor-signaling cascade, one of the most potent bone-resorbing systems. In genetic studies of 382 Japanese adult women, we found that genotypes of two promoter variations of I-TRAF gene, -1542T/G and -525G/C, were similarly associated with radial BMD levels. Two variations were in almost complete linkage disequilibrium (D' = 0.978, r(2) = 0.917, chi(2) = 695, 2, P = 3.4 x 10(-153)), and there were two exclusive haplotypes (-1542T/-525C, frequency 0.74, and -1542G/-525G, frequency 0.24) among our test subjects. When BMD values were compared among the three haplotypic categories (-1542G/-525G homozygotes, heterozygotes, and -1542T/-525C homozygotes), BMD was lowest among -1542G/-525C homozygotes (mean +/- SD = 0.382 +/- 0.060 g/cm(2)), highest among -1542T/-525G homozygotes (0.405 +/- 0.051 g/cm(2)), and intermediate among heterozygotes (0.395 +/- 0.056 g/cm(2)) (r = 0.11, P = 0.030). The observed trend supported a codominant effect of the relevant haplotype of I-TRAF gene in determination of radial BMD. These results suggested that variation of I-TRAF might be an important determinant for postmenopausal osteoporosis.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Idoxifene and estradiol enhance antiapoptotic activity through estrogen receptor-beta in cultured rat hepatocytes.

Oxidative stress plays a causative role in the development of hepatic fibrosis and apoptosis. Estradiol (E2) is an antioxidant, and idoxifene is a tissue-specific selective estrogen-receptor modulator. We have previously demonstrated that E2 inhibits hepatic fibrosis in rat models of hepatic fibrosis and that the actions of E2 are mediated through estrogen receptors (ERs). This study reports on the antiapoptotic role of idoxifene and E2, and the functions of ER subtypes ER-alpha and ER-beta in hepatocytes undergoing oxidative stress. Lipid peroxidation was induced in cultured rat hepatocytes with ferric nitrilotriacetate solution with idoxifene or E2. Oxidative stress-induced early apoptosis was linked to its ability to inhibit not only the expression of Bcl-2 and Bcl-XL but the production of antioxidant enzymes as well and to stimulate Bad expression. Hepatocytes possessed functional ER-beta, but not ER-alpha, to respond directly to idoxifene and E2. Idoxifene and E2 suppressed oxidative stress-induced reactive oxygen species generation and lipid peroxidation, and their antiapoptotic effects on the activation of activator protein-1 and nuclear factor-kappaB, the loss of antioxidant enzyme activity, and Bcl-2 family protein expression in early apoptotic hepatocytes were blocked by the pure ER antagonist ICI 182,780. Our results indicate that idoxifene and E2 could enhance antiapoptotic activity through ER-beta during oxidative damage in hepatocytes.

Animals↗
PubMed2003

Cross-reactive antigenicity of nucleoproteins of lyssaviruses recognized by a monospecific antirabies virus nucleoprotein antiserum on paraffin sections of formalin-fixed tissues.

Diagnosis of rabies is routinely confirmed by detection of rabies virus antigens in acetone-fixed frozen brain tissues or imprint smears using an immunofluorescence method with commercial antirabies virus antibodies. Since recent molecular analyses disclosed wide heterogeneity in the genome sequences of rabies virus strains and related lyssaviruses, it is necessary to confirm the presence of common epitopes in these lyssaviruses. In this study we confirmed the presence of cross-reactive antigens of various lyssaviruses in paraffin sections of formalin-fixed tissue using a monospecific rabbit antiserum prepared by immunization with a recombinant nucleoprotein of rabies virus. By immunohistochemical application, the antigen was detected predominantly in the cytoplasm of neurons in the brains of mice infected with rabies virus, Duvenhage virus, Mokola virus and European bat lyssavirus-1, while no cross-reaction was observed in uninfected humans and animals including dogs, bats, and raccoons. In addition, we examined one autopsy case that was infected in a rabies-endemic nation and developed the clinical manifestation of rabies after returning to Japan in 1970, and found that the antigen was well preserved in paraffin sections of formalin-fixed tissues. Thus, this suggests that the lyssavirus-specific antigen is recognized by the monospecific antibody against rabies virus nucleoprotein, and that this cross-reactive antigen is detectable on formalin-fixed paraffin-embedded tissues by immunohistochemical analysis.

Amino Acid Sequence↗
PubMed2003

Agitated terminal delirium and association with partial opioid substitution and hydration.

BACKGROUND: Delirium is often a distressing symptom for both patients and their families, and its prevention is important. The primary aim of this study was to clarify the effects of partial opioid substitution and hydration on the occurrence of agitated delirium in the final stage of cancer. METHODS: An historical control study on consecutive terminally ill cancer patients admitted to a palliative care unit (164 in 1996-1997 and 120 in 2000-2001). In 2000-2001, we actively performed hydration and partial opioid substitution from morphine with fentanyl on individual grounds. Two independent raters evaluated the degree of agitation and cognitive impairment during the final week, using the Memorial Delirium Assessment Scale, the Agitation Distress Scale, the Communication Capacity Scale, and a consciousness scale. RESULTS: Compared to 1996-1997, in 2000-2001, the use of artificial hydration (33% to 44%, p = 0.053) and opioid rotation (3.0% to 41%, p < 0.01) increased, while there were no statistically significant differences in hydration volume, the mean dose, and the high-dose requirements of morphine. The prevalence of agitated delirium, the agitation score, the percentage of patients achieving clear-complex communication, and the percentage of patients who maintained clear consciousness did not significantly change. CONCLUSIONS: Partial opioid substitution with fentanyl and moderate levels of hydration had no significant preventive effects on the occurrence of agitated delirium in the last week on a mass level. We should explore new strategies to prevent agitated delirium that are practically available in Japan.

Analgesics, Opioid↗
PubMed2003

Targeted gene expression using the GAL4/UAS system in the silkworm Bombyx mori.

The silkworm Bombyx mori is one of the most well-studied insects in terms of both genetics and physiology and is recognized as the model lepidopteran insect. To develop an efficient system for analyzing gene function in the silkworm, we investigated the feasibility of using the GAL4/UAS system in conjunction with piggyBac vector-mediated germ-line transformation for targeted gene expression. To drive the GAL4 gene, we used two endogenous promoters that originated from the B. mori actin A3 (BmA3) and fibroin light-chain (FiL) genes and the artificial promoter 3xP3. GFP was used as the reporter. In initial tests of the function of the GAL4/UAS system, we generated transgenic animals that carried the UAS-GFP construct plus either BmA3-GAL4 or 3xP3-GAL4. GFP fluorescence was observed in the tissues of GFP-positive animals, in which both promoters drove GAL4 gene expression. Animals that possessed only the GAL4 gene or UAS-GFP construct did not show GFP fluorescence. In addition, as a further test of the ability of the GAL4/UAS system to drive tissue-specific expression we constructed FiL-GAL4 lines with 3xP3-CFP as the transformation marker. FiL-GAL4 x UAS-GFP crosses showed GFP expression in the posterior silk gland, in which the endogenous FiL gene is normally expressed. These results show that the GAL4/UAS system is applicable to B. mori and emphasize the potential of this system for controlled analyses of B. mori gene function.

Animals↗
PubMed2003

Estrogen receptors (alpha and beta) and 17beta-hydroxysteroid dehydrogenase type 1 and 2 in thyroid disorders: possible in situ estrogen synthesis and actions.

Both epidemiological and experimental findings suggest the possible roles of sex steroids in the pathogenesis and/or development of various human thyroid disorders. In this study, we evaluated the expression of estrogen receptors (ER) alpha and beta in normal thyroid glands (N = 25; female: n = 13, male: n = 10, unknown: n = 2) ranging in age from fetus to adult. Furthermore, using immunohistochemistry, we investigated the expression of ERalpha and beta in 206 cases of thyroid disorders, including 24 adenomatous goiters, 23 follicular adenomas, and 159 thyroid carcinomas. In addition, we also studied the mRNA expression of ERalpha and beta and 17beta-hydroxysteroid dehydrogenase Type 1 and 2, enzymes involved in the interconversion between estrone and estradiol, using reverse transcription polymerase chain reaction (RT-PCR), in 48 of these 206 cases (10 adenomatous goiters, 10 follicular adenomas, and 28 papillary thyroid carcinomas) in which fresh frozen tissues were available for examination to further elucidate the possible involvement of intracrine estrogen metabolism and/or actions in thyroid disorders. ERalpha labeling index, or percentage of cells immunopositive for ERalpha, was significantly higher in adenomatous goiter (14.2 +/- 6.4), follicular adenoma (13.4 +/- 5.1), and thyroid carcinoma (16.4 +/- 2.1) than in normal thyroid gland (0; P <.05). Few follicular cells were positive for ERalpha in normal thyroid glands. In papillary carcinoma, ERalpha labeling index was significantly higher in premenopausal women (28.1 +/- 4.5) than in postmenopausal women (14.2 +/- 2.9) and in men of various ages (7.6 +/- 2.7; P <.05). In other histological types of thyroid carcinoma, no significant correlations were detected. ERbeta immunoreactivity was detected in both follicular and C-cells of normal thyroid glands, including those in developing fetal thyroid glands. In addition, ERbeta immunoreactivity was detected in the nuclei of various thyroid lesions. But no significant correlations were detected between ERbeta labeling index and clinicopathological findings including age, menopausal status, gender, and/or histological type of thyroid lesions. 17beta-hydroxysteroid dehydrogenase Type 1 expression was detected in 31/48 (64.0%) of the cases examined, whereas Type 2 was detected only in 3/46 (6.3%) of all the cases examined. These results demonstrated that estrogens may influence the development, physiology, and pathology of human thyroid glands, and these effects, especially through ERalpha, may become more pronounced in neoplasms, particularly in papillary carcinoma arising in premenopausal women.

Adenocarcinoma↗
PubMed2003

Zone-dependent expression of estrogen receptors alpha and beta in human benign prostatic hyperplasia.

Estrogen, which acts through estrogen receptors (ERs) alpha and beta, has been implicated in the pathogenesis of benign and malignant human prostatic tumors, i.e. benign prostatic hyperplasia and prostate cancer, thought to originate from different zones of the prostate [the transition zone (TZ) and peripheral zone (PZ), respectively]. Here, we examined the cellular distribution of ERalpha and ERbeta in human normal and hyperplastic prostate tissues, using in situ hybridization and immunohistochemistry. ERalpha expression was restricted to stromal cells of PZ. In contrast, ERbeta was expressed in the stromal cells of PZ as well as TZ. ERbeta-positive epithelial cells were evenly distributed in PZ and TZ of the prostate. Our results suggest that estrogen may play a crucial role in the pathogenesis of benign prostatic hyperplasia through ERbeta.

Aged↗
PubMed2003

Association of a haplotype (196Phe/532Ser) in the interleukin-1-receptor-associated kinase (IRAK1) gene with low radial bone mineral density in two independent populations.

Osteoporosis, a multifactorial common disease, is believed to result from the interplay of multiple environmental and genetic determinants, including factors that regulate bone mineral density. Interleukin-1 (IL-1) is one of the most potent bone-resorbing factors, and interleukin-1-associated kinase 1 (IRAK1) is an essential effector of the IL-1 receptor signaling cascade. In genetic studies of two independent populations of postmenopausal women (cohort A: 220 individuals and cohort T: 126 individuals) from separated geographical regions of Japan, we found that radial bone mineral density levels had similar associations with IRAK1 genotypes in both populations. Two amino acid-substituting variations in the gene, encoding Phe196Ser and Ser532Leu, were in complete linkage disequilibrium (D' = 1.0000, r2 = 1.0000, chi2 = 192.000, p = 1.2 x 10(-43)), and we found two exclusive haplotypes (196F/532S, frequency 0.74; 196S/532L, frequency 0.26) of the IRAK1 gene among our test subjects. In both populations, a significant association with decreased radial bone mineral density was identified with haplotype 196F/532S (in cohort A: r = 0.21, p = 0.0017; in cohort T: r = 0.23, p = 0.011). Radial bone mineral density was lowest among 196F/532S homozygotes, highest among 196S/532L homozygotes, and intermediate among heterozygotes. Accelerated bone loss also correlated with the 196F/532S haplotype in a 5-year follow-up. These results suggest that variation of IRAK1 may be an important determinant of postmenopausal osteoporosis, in part through the mechanism of accelerated postmenopausal bone loss.

Base Sequence↗
PubMed2003

Association of molecular variants, haplotypes, and linkage disequilibrium within the human vitamin D-binding protein (DBP) gene with postmenopausal bone mineral density.

UNLABELLED: Possible contribution of vitamin D-binding protein (DBP) gene for determination of BMD was tested by characterizing 13 SNPs in 384 adult Japanese women. When the effect of a specific single SNP was tested, five SNPs (-39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) correlated with BMD significantly at various levels. The chromosomal dosage of one haplotype (T-C-C-G-T-C in -39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E, and IVS11+1097G>C) displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Multiple regression analyses revealed a most significant correlation with the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis. INTRODUCTION: Osteoporosis results from the interplay of multiple environmental and genetic determinants. The gene encoding vitamin D-binding protein (DBP), a key factor for regulating calcium homeostasis through the vitamin D endocrine system, is a probable candidate for conferring susceptibility to osteoporosis. METHODS: To test a possible contribution of the DBP gene for determination of bone mineral density (BMD) of adult women, we have characterized 13 single nucleotide polymorphisms (SNPs) within the DBP gene in DNA from 384 adult Japanese women and attempted to correlate specific SNPs with BMD. RESULTS AND CONCLUSIONS: Sixteen major haplotypes accounted for 80% of the variations, indicating allelic complexity in this genomic region. Pairwise linkage disequilibrium (LD), measured by the D' and r2 statistics, demonstrated a general pattern of decline with increasing distance, but individual LD values within small genomic segments were diverse. Regression analysis for adjusted BMD revealed significant correlation with respect to five of them (-39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) at various levels. An intronic SNP (IVS11+1097G>C) with the highest significance of association (p = 0.006) showed significant LD with four SNPs located around the first exon (r2 values > 0.18, D' > 0.5). A non-synonymous coding SNP, D432E, showed a comparable level of correlation, but it was in a moderate LD only with IVS11+1097G>C. The chromosomal dosage of one haplotype (T-C-C-G-T-C in -39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E and IVS11+1097G>C) estimated in each subject displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Furthermore, multiple regression analyses revealed that the most significant correlation was achieved for the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis.

Aged↗