Relationship between vitamin D receptor gene polymorphisms (BsmI, TaqI, ApaI, and FokI) and calcium intake on bone mass in young Japanese women.

BACKGROUND: The high prevalence of low bone mass in young women in Japan has emerged as a serious health issue in recent years. Therefore, the aim of the present study was to reevaluate the relationship between genetic and dietary factors, as well as its influence on bone mass in young Japanese women, with particular emphasis on vitamin D receptor (VDR) gene polymorphisms and calcium intake. METHODS: A total of 499 Japanese women aged 20-24 years were enrolled in the study. The bone mass of the calcaneus was assessed using the quantitative ultrasound method and expressed as the osteo sono-assessment index (OSI). VDR gene polymorphisms (BsmI, TaqI, ApaI, and FokI) were analyzed using DNA extracted from saliva. Calcium intake was assessed using the Food Frequency Questionnaire based on food groups (FFQg) and adjusted with the energy intake. Participants were divided into two groups based on the median calcium intake (250 mg/1000 kcal). RESULTS: Consequently, bone mass was significantly different among the BsmI and TaqI genotypes after adjusting for body mass index (BMI) (p = 0.030 and 0.019, respectively). In addition, the BsmI AA and ApaI GT genotypes showed significant differences in bone mass between the calcium-intake groups, with low OSI in the low-calcium intake group and high OSI in the high-calcium intake group, respectively, even after adjusting for BMI (p = 0.020 and 0.038, respectively). CONCLUSIONS: These findings may prove instrumental in developing a logical approach towards preventing bone loss in young Japanese women.

Effect of Cdx2 Polymorphism on the Relationship between Dietary Calcium Intake and Peak Bone Mass in Young Japanese Women.

Studies investigating the effect of the caudal-type homeobox protein 2 (Cdx2) polymorphism in the vitamin D receptor gene and calcium intake on bone mass have shown inconsistent results. This study investigated whether the effect of calcium intake on peak bone mass is affected by Cdx2 polymorphism in young Japanese women. A cross-sectional study of 500 young women was conducted. Dietary intake was assessed by the Food Frequency Questionnaire. The osteo sono-assessment index (OSI), assessed by the qualitative ultrasound method, was used as a bone mass index. The subjects were divided into two groups by the median calcium intake. The OSI was not different among Cdx2 genotypes and between calcium groups (p = 0.960, p = 0.191, respectively). The interaction between calcium and Cdx2 genotypes on the OSI approached significance (GG versus GA and AA genotypes, p = 0.092). The difference in the OSI between calcium groups was significant in the GG genotype (p = 0.028), but not in the GA or AA genotypes (p = 0.501, p = 0.306, respectively). Adjustment for covariates (body mass index and physical activity) did not change the results. In conclusion, the relationship between dietary calcium intake and peak bone mass may vary according to Cdx2 polymorphism.

Short-term and long-term ketogenic diet therapy and the addition of exercise have differential impacts on metabolic gene expression in the mouse energy-consuming organs heart and skeletal muscle.

Although a ketogenic diet (KD) is used to treat various metabolic diseases, the organ-specific metabolic changes that occur in response to a KD remain unclear. Therefore, we tested the hypothesis that duration of KD consumption and regular exercise in addition to KD consumption affect metabolic fuel selection at gene levels in heart and skeletal muscle. Six-week-old male C57BL/6J mice were divided into 2 groups, one fed a standard diet and the other fed a KD, and maintained for either 4 weeks (short term) or 12 weeks (long term). The long-term group was further divided into 2 subgroups, and mice in 1 of the 2 groups had an exercise load 5 days a week. Body weight decreased significantly in the KD groups during the first few weeks only. Plasma ketone levels rose and muscle glycogen levels declined significantly in the KD groups, but these changes were less severe in the KD plus exercise group. KD consumption decreased the expression of genes related to glucose utilization in heart and skeletal muscle; however, this decrease did not occur with KD consumption plus exercise. Long-term but not short-term KD consumption increased the expression of genes related to lipid utilization, regardless of exercise. In the KD groups, the expression of genes related to ketolysis was suppressed, and that of genes related to ketogenesis was increased. These results indicate that KD exposure and pairing a KD with exercise have differential impacts on energy substrate selection at gene expression levels in energy-consuming organs, the heart and skeletal muscle.

Vitamin D receptor gene polymorphism is associated with chronic periodontitis.

Chronic periodontitis (CP) is caused by enhanced resorption of the alveolar bone supporting the teeth and is associated with intraoral inflammation after infection with certain bacteria. The VDR gene polymorphism was reported recently to be deeply related to the occurrence of tuberculosis and infection of chronic hepatitis B virus. This may be interpreted to indicate a close relationship between VDR gene polymorphism and the immunological action, because vitamin D activates monocytes, stimulates cell-mediated immunity, and suppresses lymphocyte proliferation. The purpose of the present study was to clarify whether polymorphisms in VDR gene exons are associated with the incidence of CP. A case-controlled study was performed on a group of 168 unrelated Japanese subjects whose ages ranged from 35 to 65 years. The Taq I polymorphism in the VDR gene was found to be associated significantly with CP (X2=4.48, P=0.034). We performed multiple logistic regression analyses on the TT genotype, which was found to be associated with CP, and on well-recognized risk factors, smoking and diabetes. The odds ratio (OR) for the genotype (TT/Tt) was 2.73 (95% CI 1.11-6.68, P=0.028), being larger than the unadjusted value. This indicates that the VDR gene polymorphism (TT genotype) is a risk factor for CP, independently of smoking and diabetes.

Bone morphogenetic protein-4 gene polymorphism and early marginal bone loss around endosseous implants.

PURPOSE: At stage II surgery during dental implant treatment, early marginal bone loss around the implant occasionally occurs despite a lack of apparent causal events, and the etiology of this bone loss is unclear. This study was designed to investigate whether the bone morphogenetic protein-4 (BMP-4) genetic polymorphism is associated with early marginal bone loss around implants. MATERIALS AND METHODS: The BMP-4 polymorphism was detected by restriction fragment length analysis using HphI digestion after polymerase chain reaction. A total of 262 implants were placed in 41 patients, and early marginal bone loss was observed in 25 of the 109 maxillary implants and 14 of the 153 mandibular implants. RESULTS: In the mandible, the patients with the BMP-4 AV genotype had a significantly higher rate of occurrence of marginal bone loss than those with the BMP-4 W genotype (P = .012). According to multiple logistic regression analyses, the odds ratio of the AV versus the W BMP-4 genotype was 8.106 between patients with and those without bone loss in the mandible (95% CI = 1.30 to 50.51; P = .025). DISCUSSION: These results suggest that the BMP-4 genetic polymorphism influences early marginal bone loss around implants. CONCLUSION: While perhaps premature in recommendation, genetic screening before implant surgery may prove to be a very useful aid to consider the risk of implant treatment.

Genetic polymorphisms of the interleukin-1 gene and early marginal bone loss around endosseous dental implants.

Dental implant surgery commonly proceeds in two stages. It is generally accepted that bone loss around implants does not occur at stage-II surgery because implants do not receive mechanical loading. However, early marginal bone loss around implants occasionally does occur during the healing period. Genetic polymorphisms in the interleukin-1 (IL-1) gene have been reported to be important for bone homeostasis and susceptibility to bone disease. We therefore investigated whether the idiopathic early marginal bone loss around implants is related to polymorphisms in the IL-1 gene. We performed a case-control study. Patients demonstrating marginal bone loss around implants at stage-II surgery were designated as the 'marginal bone loss (+)' group and those without bone loss as the 'marginal bone loss (-)' group. Polymorphisms of the IL-1alpha and IL-1beta genes (IL-1A-889, IL-1B-511 and IL-1B+3954) were detected by restriction fragment length polymorphism using NcoI, AvaI and TaqI after polymerase chain reactions. A total of 251 implants were placed in 39 patients. Marginal bone loss was observed in 36 implants. The patients with IL-1B-511 2/2 genotype exhibited a significantly higher occurrence of marginal bone loss than those with IL-1B-511 1/1 or 1/2 genotypes (OR=5.63; 95% CI=1.20-26.42; P=0.033). Multiple logistic regression analyses showed a markedly increased odds ratio (OR=10.86; 95% CI=1.64-71.90) in IL-1B-511 2/2 genotype carriers, while ORs of the other risk factors for bone loss, such as age, smoking status, post-menopausal women and bone quality, remained between 0.44 and 6.20. There was no significant difference in the distributions of the IL-1B+3954 and IL-1 A-889 genotypes between cases and controls. These data suggest that the IL-1B-511 2/2 genotype has a significant association with the incidence of early marginal bone loss around endosseous implants.

Association of calcitonin receptor gene polymorphism with early marginal bone loss around endosseous implants.

PURPOSE: This study investigated the relationship between calcitonin receptor (CTR) genotype and buccal marginal bone loss observed at stage II surgery for endosseous implants. MATERIALS AND METHODS: A total of 237 implants were placed in 35 patients; 89 implants were placed in maxillae and 148 implants in mandibles. The CTR genetic polymorphism was examined by the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: Patients with the TC genotype were 20 times more likely to suffer buccal marginal bone loss in the mandible than patients with the CC genotype. Furthermore, there were no significant differences in the distribution of age, smoking status, postmenopausal women, and bone quality between patients with and without bone loss in either jaw. DISCUSSION: These results suggest that the known risk factor for bone loss cannot explain the early marginal bone loss around the implants. CONCLUSION: Although further genetic research should be conducted, it is suggested that the CTR genetic test could become a useful tool in the planning of treatment before implant surgery and lead to more predictable implant treatment.