Nucleotide Polymorphisms Of Vitamin Research Articles

Single nucleotide polymorphisms in vitamin D binding protein and 25-hydroxylase genes affect vitamin D levels in adolescents of Arab ethnicity in Kuwait.

Vitamin D deficiency (VDD) is widespread in the Arab world despite ample sunshine throughout the year. In our previous study, lifestyle and socio-demographic factors could explain only 45% of variability in vitamin D levels in Kuwaiti adolescents, suggesting that genetics might contribute to VDD in this region. Single nucleotide polymorphisms (SNP) in the 25-hydroxylase (CYP2R1) and the GC globulin (GC) genes have been reported to affect vitamin D levels in various ethnic groups in adults. In this study, we investigated the association of two SNPs from GC (rs4588 and rs7041) and three SNPs from CYP2R1 (rs10741657, rs11023374 and rs12794714) with vitamin D levels and VDD in a nationally representative sample of adolescents of Arab ethnicity from Kuwait. Multivariable linear regression, corrected for age, sex, parental education, governorate, body mass index, and exposure to sun, demonstrated that each of the 5 study variants showed significant associations with plasma 25(OH)D levels in one or more of the additive, recessive, and dominant genetic models - the rs10741657 under all the three models, rs12794714 under both the additive and recessive models, rs7041 under the recessive model; and rs4588 and rs11023374 under the dominant model. Minor alleles at rs4588 (T), rs7041 (A), rs11023374 (C), and rs12794714 (A) led to a decrease in plasma 25(OH)D levels - rs4588:[β (95%CI) = -4.522 (-8.66,-0.38); p=0.033]; rs7041:[β (95%CI) = -6.139 (-11.12,-1.15); p=0.016]; rs11023374:[β (95%CI) = -4.296 (-8.18,-0.40); p=0.031]; and rs12794714:[β (95%CI) = -3.498 (-6.27,-0.72); p=0.014]. Minor allele A at rs10741657 was associated with higher levels of plasma 25(OH)D levels [β (95%CI) = 4.844 (1.62,8.06); p=0.003)] and lower odds of vitamin D deficiency (OR 0.40; p=0.002). These results suggest that the CYP2R1 and GC SNP variants are partly responsible for the high prevalence of VDD in Kuwait. Genotyping these variants may be considered for the prognosis of VDD in Kuwait.

Leptin and IGF-1 in Infancy Are Associated With Variants in DHCR7 and CYP2R1 That Relate With Type 1 Diabetes and 25OHD.

Vitamin D has been variably implicated in risk of developing type 1 diabetes based on cohorts of at-risk individuals. Emergent type 1 diabetes in childhood is putatively preceded by altered growth. We explored whether polymorphisms in vitamin D metabolism genes modify risk of type 1 diabetes via effects on growth in a prospective, population-based cohort of infants. The Cambridge Baby Growth Study enrolled newborns from Cambridgeshire, UK, for follow-up in infancy. In 612 infants, we genotyped single nucleotide polymorphisms in vitamin D metabolism genes that relate with type 1 diabetes: rs10741657 and rs12794714 in CYP2R1, rs12785878 in DHCR7, and rs10877012 in CYP27B1. Multivariate linear regression analyses tested associations between genotypes and anthropometric indices (weight, length, and skinfold thickness) or growth-related hormones (C-peptide, IGF-1, and leptin) in infancy. Birth weight showed borderline associations with the diabetes risk-increasing alleles in CYP2R1, rs10741657 (β = -.11, P = .02) and rs12794714 (β = -.09, P = .04). The risk-increasing allele rs12794714 was also associated with higher IGF-1 levels at age 24 months (β = .30, P = .01). At age 3 months, the risk-increasing allele rs12785878 in DHCR7, known to negatively associate with 25-hydroxyvitamin D levels, showed a positive association with leptin levels (β = .23, P = .009), which was pronounced in girls (P = .004) vs boys (P = .7). The vitamin D metabolism genes DHCR7 and CYP2R1 might influence infancy leptin and IGF-1 levels respectively. These findings open the possibility for a developmental role of vitamin D that is mediated by growth-related hormones with implications for the onset of type 1 diabetes autoimmunity.

Vitamin C Urinary Loss in Fabry Disease: Clinical and Genomic Characteristics of Vitamin C Renal Leak

BackgroundReduced plasma vitamin C concentrations in chronic diseases may result from abnormal urinary excretion of vitamin C: a renal leak. We hypothesized that vitamin C renal leak may be associated with disease-mediated renal dysregulation, resulting in aberrant vitamin C renal reabsorption and increased urinary loss. ObjectivesWe investigated the prevalence, clinical characteristics, and genomic associations of vitamin C renal leak in Fabry disease, an X-linked lysosomal disease associated with renal tubular dysfunction and low plasma vitamin C concentrations. MethodsWe conducted a non-randomized cross-sectional cohort study of men aged 24–42 y, with Fabry disease (n = 34) and controls without acute or chronic disease (n = 33). To match anticipated plasma vitamin C concentrations, controls were placed on a low-vitamin C diet 3 wk before inpatient admission. To determine the primary outcome of vitamin C renal leak prevalence, subjects were fasted overnight, and matched urine and fasting plasma vitamin C measurements were obtained the following morning. Vitamin C renal leak was defined as presence of urinary vitamin C at plasma concentrations below 38 μM. Exploratory outcomes assessed the association between renal leak and clinical parameters, and genomic associations with renal leak using single nucleotide polymorphisms (SNPs) in the vitamin C transporter SLC23A1. ResultsCompared with controls, the Fabry cohort had 16-fold higher odds of renal leak (6% vs. 52%; OR: 16; 95% CI: 3.30, 162; P < 0.001). Renal leak was associated with higher protein creatinine ratio (P < 0.01) and lower hemoglobin (P = 0.002), but not estimated glomerular filtration rate (P = 0.54). Renal leak, but not plasma vitamin C, was associated with a nonsynonymous single nucleotide polymorphism in vitamin C transporter SLC23A1 (OR: 15; 95% CI: 1.6, 777; P = 0.01). ConclusionsIncreased prevalence of renal leak in adult men with Fabry disease may result from dysregulated vitamin C renal physiology and is associated with abnormal clinical outcomes and genomic variation.

Association of udder type traits with single nucleotide polymorphisms in Sahiwal (Bos indicus) and Karan Fries (Bos taurus × Bos indicus) cattle

Udder structure of milking cows is not merely vital to display the visual characteristics, but also important for high milk output and low mastitis risk incidence as well. The present study measured different udder type traits in Sahiwal (Bos indicus) and Karan Fries (Bos taurus × Bos indicus) and investigated their association with single nucleotide polymorphisms in Vitamin D Receptor and Protein Tyrosine Phosphatase, Receptor Type, R genes. GG genotype of SNP rs454303072 was found to have wider rear udder, larger udder circumference, longer distance between fore-rear teats and left-right teats in Karan Fries cattle. Whereas, in Sahiwal cattle, AA genotype of this SNP was found to be associated with the higher and wider rear udder, larger udder circumference and wider udder. AA genotype of SNP rs382671389 was found to be associated with longer fore teat in Karan Fries cattle. The TT and CC genotype of SNP rs435289107 was associated with udder type traits in Karan Fries and Sahiwal cattle respectively. These results suggest that BTA 5 harbors genomic regions associated with udder traits in Bos indicus and Bos indicus x Bos taurus cattle.

Vitamin C Urinary Loss in Fabry Disease: Clinical and Genomic Factors of Vitamin C Renal Leak

ObjectivesReduced plasma vitamin C concentrations in chronic diseases may result from abnormal urinary excretion of vitamin C excretion: a renal leak. We hypothesized that vitamin C renal leak may be the consequence of disease-mediated dysregulation affecting the renal tubules, resulting in aberrant vitamin C renal reabsorption and increased urinary loss. The study objective was to investigate the prevalence, clinical characteristics, and genomic associations of vitamin C renal leak in Fabry disease, an X-linked lysosomal storage disease associated with renal tubular dysfunction and low plasma vitamin C concentration.MethodsThis was a non-randomized cross-sectional cohort study of males with Fabry disease (n = 34) and healthy male controls (n = 33). To determine primary outcome of vitamin C renal leak, matched urine and fasting plasma vitamin C measurements were obtained following an overnight fast. Based on data from healthy men, vitamin C renal leak was defined as presence of urinary vitamin C at plasma concentrations below 38 µM. Exploratory outcomes assessed the association between renal leak and clinical parameters; and genomic associations with renal leak using single nucleotide polymorphisms (SNPs) in the vitamin C transporter SLC23A1. Proof-of-concept studies were conducted using two mouse models.ResultsCompared with healthy men, Fabry cohort had 16-fold higher odds of renal leak (6% vs 52%: OR16, P < 0.001). Renal leak was associated with higher protein creatinine ratio (p = 0.01), lower hemoglobin (p = 0.002) and hematocrit (p = 0.008). Renal leak, but not plasma vitamin C, was associated with a non-synonymous single nucleotide polymorphism in vitamin C transporter SLC23A1 (p = 0.01 and p = 0.47 respectively). Using two mouse models, we recapitulated the relationships between renal leak, dysregulated vitamin C renal reabsorption and low plasma vitamin C concentrations.ConclusionsIncreased prevalence of vitamin C renal leak in Fabry disease may result from dysregulated vitamin C renal physiology, with significant clinical and genomic associations. Renal leak may be more sensitive than plasma vitamin C in evaluating genomic associations in small cohorts.Funding SourcesIntramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda MD 20,892–1372.

The role of 25-hydroxyvitamin-D3 and vitamin D receptor gene in human periodontal ligament fibroblasts as response to orthodontic compressive strain: an in vitro study

BackgroundThis study aimed to investigate, if different physiological concentrations of vitamin D (25(OH)D3) and single nucleotide polymorphisms in vitamin D receptor (VDR) gene have an impact on gene expression in human periodontal ligament (hPDL) fibroblasts induced by simulated orthodontic compressive strain.MethodsA pool of hPDL fibroblasts was treated in absence or presence of 25(OH)D3 in 3 different concentrations (10, 40 and 60 ng/ml). In order to evaluate the role of single nucleotide polymorphisms in the VDR gene, hPDL fibroblasts from 9 patients were used and treated in absence or presence of 40 ng/ml 25(OH)D3. Each experiment was performed with and without simulated orthodontic compressive strain. Real-time PCR was used for gene expression and allelic discrimination analysis. Relative expression of dehydrocholesterol reductase (DHCR7), Sec23 homolog A, amidohydrolase domain containing 1 (AMDHD1), vitamin D 25-hydroxylase (CYP2R1), Hydroxyvitamin D-1-α hydroxylase, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2) and interleukin-6 (IL6) was assessed. Three single nucleotide polymorphisms in VDR were genotyped. Parametric or non-parametric tests were used with an alpha of 5%.ResultsRANKL, RANKL:OPG ratio, COX-2, IL-6, DHCR7, CYP2R1 and AMDHD1 were differentially expressed during simulated orthodontic compressive strain (p < 0.05). The RANKL:OPG ratio was downregulated by all concentrations (10 ng/ml, 40 ng/ml and 60 ng/ml) of 25(OH)D3 (mean = 0.96 ± 0.68, mean = 1.61 ± 0.66 and mean = 1.86 ± 0.78, respectively) in comparison to the control (mean 2.58 ± 1.16) (p < 0.05). CYP2R1 gene expression was statistically modulated by the different 25(OH)D3 concentrations applied (p = 0.008). Samples from individuals carrying the GG genotype in rs739837 presented lower VDR mRNA expression and samples from individuals carrying the CC genotype in rs7975232 presented higher VDR mRNA expression (p < 0.05).ConclusionsSimulated orthodontic compressive strain and physiological concentrations of 25(OH)D3 seem to regulate the expression of orthodontic tooth movement and vitamin-D-related genes in periodontal ligament fibroblasts in the context of orthodontic compressive strain. Our study also suggests that single nucleotide polymorphisms in the VDR gene regulate VDR expression in periodontal ligament fibroblasts in the context of orthodontic compressive strain.

The association between single nucleotide polymorphism in vitamin D receptor and calcium oxalate urolithiasis in dogs.

BackgroundPolymorphisms of the vitamin D receptor (VDR) are associated with calcium oxalate (CaOx) nephrolithiasis in humans.ObjectivesTo investigate the association between VDR polymorphisms and susceptibility to CaOx urolithiasis in dogs.AnimalsThirty‐five dogs with CaOx urolithiasis were compared with 40 stone‐free dogs.MethodsThis was a case‐control study. Two VDR gene polymorphisms (rs851998024 and rs852900542) were detected by specific TaqMan real‐time polymerase chain reaction assay, and their relationship with serum 1,25‐dihydroxyvitamin D, serum and urinary electrolyte concentrations was evaluated.ResultsThe distribution of the rs852900542 polymorphism was significantly different between the case and the control dogs (x 2 = 6.369, P = .04). Dogs with a CC or CT genotype had an increased risk of CaOx stones than those with the TT genotype (odds ratio = 3.82, 95% confidence interval 1.04‐13.98). The CaOx dogs with the TT genotype had a significantly lower urinary calcium‐to‐creatinine ratio than the CT+CC genotypes. 1,25‐(OH)2D concentrations did not differ between the cases and the controls (308.7 ± 217.4 vs 286.7 ± 185.1 pg/mL, P = .45).Conclusions and Clinical ImportanceThis finding suggests that vitamin D metabolism might play a role in CaOx stone formation in dogs.

Single Nucleotide Polymorphisms in Vitamin D Receptor Gene Affect Birth Weight and the Risk of Preterm Birth: Results From the "Mamma & Bambino" Cohort and A Meta-Analysis.

The effect of vitamin D receptor gene (VDR) polymorphisms on adverse pregnancy outcomes—including preterm birth (PTB), low birth weight and small for gestational age—is currently under debate. We investigated 187 mother-child pairs from the Italian “Mamma & Bambino” cohort to evaluate the association of maternal VDR polymorphisms—BsmI, ApaI, FokI and TaqI—with neonatal anthropometric measures and the risk of PTB. To corroborate our results, we conducted a meta-analysis of observational studies. For the FokI polymorphism, we showed that gestational duration and birth weight decreased with increasing number of A allele (p = 0.040 and p = 0.010, respectively). Compared to the GG and GA genotypes, mothers who carried the AA genotype exhibited higher PTB risk (OR = 12.049; 95% CI = 2.606–55.709; p = 0.001) after adjusting for covariates. The meta-analysis confirmed this association under the recessive model (OR = 3.67, 95%CI 1.18–11.43), and also pointed out the protective effect of BsmI polymorphism against the risk of PTB under the allelic (A vs. G: OR = 0.74; 95%CI 0.59–0.93) and recessive (AA vs. GG + AG: OR = 0.62; 95%CI 0.43–0.89) models. Our results suggest the association between some maternal VDR polymorphisms with neonatal anthropometric measures and the risk of PTB.

BSMI single nucleotide polymorphism in vitamin D receptor gene is associated with decreased circulatory levels of serum 25-hydroxyvitamin D among micro and macrovascular complications of type 2 diabetes mellitus

Vitamin D Receptor (VDR) gene single nucleotide polymorphism (SNP) in the intron 8 is a well characterized SNP which has previously been linked to various diseases including Type 2 Diabetes Mellitus (T2DM). However, the association of this SNP with micro and macrovascular complications of T2DM remains poorly studied. Hence, the present study was designed to investigate the association of VDR gene SNP with complications of T2DM (disease phenotype) and correlated it with the serum levels of (25[OH]D) (intermediate phenotype) along with other clinical risk factors of T2DM. Genotyping was carried out in a total of 866 subjects, in which Group-I had Control subjects (n = 252), Group-II with T2DM without complications (n = 200); Group-III and Group-IV had subjects with micro (n = 216) and macrovascular (n = 198) complications respectively by PCR -RFLP. The ‘G' allele of the VDR gene SNP is associated with a significant risk for T2DM, Diabetic Neuropathy (DN) and Coronary Artery Disease (CAD). In addition, subjects with mutant GG genotype had lower levels of (25[OH]D) in both T2DM and micro-macrovascular complications than AA genotype. Thus, VDR (rs1544410) SNP was found to be associated with decreased serum (25[OH]D) levels in both micro-macrovascular complications of T2DM among South Indian Population.

Associations between single nucleotide polymorphisms in vitamin D metabolic pathway genes and serum 25(OH)D concentrations in Brazilian adults: the Pró‐Saúde Study

Vitamin D status is influenced by a number of factors including dietary intake, skin pigmentation and sun exposure. Serum concentration of 25(OH)D may also be under the influence of polymorphisms in genes functionally important for vitamin D metabolism. The aim of our study was to explore the association between rs12785878 (NADSYN1), rs6013897 (CYP24A1), rs10741657 (CYP2R1) and rs2282679 (GC) polymorphisms and serum concentrations of vitamin D in an adult Brazilian population. We evaluated 514 participants (33–79 yrs; 266 women, 248 men) with the Pró‐Saúde Study, a cohort of university employees in Rio de Janeiro (22°57′S), Brazil. Serum 25(OH)D concentrations were analyzed by chemiluminescent enzyme‐labeled immunometric assay. Genotyping of common variants were performed by real time PCR method. Mean serum 25(OH)D was 19.4 (SD: 8.1 ng/mL) and 54% of participants had concentrations below 20ng/ml. Allele frequencies were G (54%) and T (46%) for rs12785878; T (65%) and A (35%) for rs6013897; G (71%) and A (29%) for rs10741657; and T (78%) and G (22%) for rs2282679. Both genotype and allele frequencies for rs2282679 showed statistically significant differences (p=0.001 and p=0.0003, respectively) between groups according to vitamin D sufficiency (&lt;20ng/mL vs. ≥20ng/ml). The allelic association analysis showed that rs2282679 G allele was a risk factor for vitamin D insufficiency [serum 25(OH)D &lt;20ng/mL, OR=1.75 (1.29–2.38)]. After adjustments for month of blood drawn, skin type, sun exposure index and vitamin D intake, participants homozygous for the ancestral allele (TT) for rs2282679 had significantly higher serum 25(OH)D than TG and GG genotypes (mean±SE: 20.5±0.5, 17.7±0.6 and 17.0±1.5, respectively, p=0.001). Our results suggest that rs2282679 polymorphisms may contribute to variability in serum 25(OH)D concentrations in Brazilian adults, and therefore should be considered when evaluating determinants of vitamin D status, as well when interpreting results on prevalence of vitamin D insufficiency in this population.Support or Funding InformationConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, grant number 484636/2013‐8) and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, grant number 26/102.201/2013), Brazil

Association between Single Nucleotide Polymorphisms in Vitamin D Receptor Gene Polymorphisms and Permanent Tooth Caries Susceptibility to Permanent Tooth Caries in Chinese Adolescent.

Purpose Dental caries is a multifactorial infectious disease. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR) gene were associated with susceptibility to permanent tooth caries in Chinese adolescents. Method A total of 200 dental caries patients and 200 healthy controls aged 12 years were genotyped for VDR gene polymorphisms using the PCR-restriction fragment length polymorphism (PCR-RFLP) assay. All of them were examined for their oral and dental status with the WHO criteria, and clinical information such as the Decayed Missing Filled Teeth Index (DMFT) was evaluated. Genomic DNA was extracted from the buccal epithelial cells. The four polymorphic SNPs (Bsm I, Taq I, Apa I, and Fok I) in VDR were assessed for both genotypic and phenotypic susceptibilities. Results Among the four examined VDR gene polymorphisms, the increased frequency of the CT and CC genotype of the Fok I VDR gene polymorphism was associated with dental caries in 12-year-old adolescent, compared with the controls (X2 = 17.813, p ≤ 0.001). Moreover, Fok I polymorphic allele C frequency was significantly increased in the dental caries cases, compared to the controls (X2 = 14.144, p ≤ 0.001, OR = 1.730, 95% CI = 1.299–2.303). However, the other three VDR gene polymorphisms (Bsm I, Taq I, and Apa I) showed no statistically significant differences in the caries groups compared with the controls. Conclusion VDR-Fok I gene polymorphisms may be associated with susceptibility to permanent tooth caries in Chinese adolescent.

Responses of Total and Bioavailable 25‐Hydroxyvitamin D and Factors Modifying the Responses: A Randomized, Placebo‐Controlled Trial of Vitamin D3 Supplementation in an Asian Population

Vitamin D deficiency, defined as circulating 25‐hydroxyvitamin D [25(OH)D&lt;50 nmol/L], is a common nutrition problem globally. Ethnic differences were noticed in vitamin D status and related health outcomes. However, little is known about how genetic and other factors influence vitamin D metabolism in Asians despite of having the world largest population. Recently, we have conducted two randomized clinical trials. One of them (n=76) was a 5‐arm, dose‐response study to evaluate effects of daily administration from 400 IU (Chinese Recommended Dietary Allowance) to 2000 IU (Chinese tolerable Upper Intake Level) of vitamin D3 on serum 25(OH)D levels. After 16 week, only 80% of participants in 2000 IU group achieved the Institute of Medicine targeted level of 50 nmol/L. In another recent 2‐arm trial, we further investigated: 1) responses of total and bioavailable 25(OH)D, defined as fraction of circulating 25(OH)D unbound to vitamin D binding protein (VDBP); and 2) effects of personal and genetic factors on the responses. A total of 448 participants with vitamin D deficiency were randomly assigned to placebo or treatment arm (2000 IU/d vitamin D3). Serum 25(OH)D, VDBP, iPTH, calcium were measured at week 0, 10 and 20. Bioavailable 25(OH)D was calculated by validated formulas. Six single nucleotide polymorphisms in vitamin D pathway genes (GC, VDR, DHCR7, CYP2R1, CYP24A1) were genotyped. After 20 weeks, the mean (SD) of total 25(OH)D increased from 32.3(8.7) nmol/L and 32.9(8.9) nmol/L to 36.3(9.8) nmol/L and 67.3(23.1) nmol/L; while the mean bioavailable 25(OH)D increased from 7.0(3.5) nmol/L and 7.3(4.1) nmol/L to 7.6(4.1) nmol/L and 14.7(8.3) nmol/L in placebo and treatment arm, respectively (all Pbetweengroups&lt;0.001). Approximately 75% of participants in treatment arm achieved 25(OH)D of 50 nmol/L at week 20. Mean (SE) VDBP levels at baseline were 165.3(4.3) ug/ml and remained steady through the trial. The responses of total or bioavailable 25(OH)D to vitamin D3 supplement were modified by variants in GC and VDR (P≤0.03). Interestingly, there was significant interaction between GC rs7041 genotypes and treatment in bioavailable 25(OH)D response (Pinteraction&lt;0.001), but not in total 25(OH)D response. Other determinants for the responses of total and bioavailable 25(OH)D included their baseline values, gender and BMI [only total 25(OH)D response]. Compared with previously reported VDBP level (337±5 ug/ml) in white American, our participants showed substantially lower VDBP levels, which is apparently attributed to higher prevalence of GC rs7041‐T, thereby raised bioavailable 25(OH)D levels. To our best knowledge, this study is the first trial determining the responses of total and bioavailable 25(OH)D and modifying factors on the responses. Findings of unique combinations of genetic polymorphisms and VDBP profile in Chinese, implicates that different cut‐off points might be needed to define vitamin D status and also to modify current recommendation for Asians.Support or Funding InformationThis study was supported by Ministry of Science and Technology of China [2013BAI04B03], and the National Natural Science Foundation of China [81170734, 81321062].

Tu1375 Strong Association of Single Nucleotide Polymorphisms of Vitamin D Receptor Gene, BsmI, and Colorectal Cancer in Asian Population

Tu1375 Strong Association of Single Nucleotide Polymorphisms of Vitamin D Receptor Gene, BsmI, and Colorectal Cancer in Asian Population

Correlating single nucleotide polymorphisms in vitamin D metabolism-related genes to autism susceptibility and vitamin D treatment: study protocol of a non-randomized parallel-cohort controlled trial

Background: Vitamin D plays a unique role in promoting embryonic and neural development, cerebral immunological regulation, and influencing neural differentiation and gene regulation. Vitamin D deficiency may be one of the environmental risk factors for autism spectrum disorder. This trial has two purposes: (1) correlating single nucleotide polymorphisms of vitamin D metabolism-related key enzymes to autism susceptibility; and (2) investigating the therapeutic effect of exogenous vitamin D on autism spectrum disorder. Methods/Design: A non-randomized parallel-cohort controlled trial. Sixty children with autism spectrum disorder who receive treatment at the Department of Pediatric Neurological Rehabilitation, First Hospital, Jilin University, China, are included. Sixty healthy controls are also recruited from those undergoing a physical examination. For the first purpose, primary outcomes include vitamin D metabolism and single nucleotide polymorphisms of related genes. Vitamin D level in peripheral blood is the secondary outcome. For the second purpose, 60 children with autism spectrum disorder are treated with exogenous vitamin D supplementation. Prior to and 1 month after exogenous vitamin D supplementation, primary outcomes are evaluated, including the Childhood Autism Rating Scale (CARS) score, Autism Behavior Checklist (ABC) score, the Gesell Developmental Schedules (GDS) score, Clinical Global Impression Scale-(CGI) for severity of illness (SI), global improvement (GI), and efficacy index (EI) scores. Again, vitamin D levels in peripheral blood are evaluated as the secondary outcome. Discussion: This trial is sufficiently powered to provide scientific evidence for the genetic and pathological mechanism of autism spectrum disorder in children that lack vitamin D. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) identifier: ChiCTR-TRC-14004499; registered on 30 November 2013. Ethical issues: This trial was approved by the Medical Ethics Committee, First Hospital of Jilin University, China (approval No. 2013-192). The trial protocol will be performed in accordance with the Declaration of Helsinki.

Single nucleotide polymorphisms of vitamin D binding protein, vitamin D receptor and retinoid X receptor alpha genes and response to hepatitis B vaccination in renal replacement therapy patients

Aim: Vitamin D (VD) was recently associated with response to hepatitis B vaccination in chronic kidney disease. We investigated whether polymorphisms in VD binding protein (GC), VD receptor (VDR) and retinoid X receptor α (RXRA) genes were associated with response to hepatitis B vaccination in renal replacement therapy (RRT) patients. Method: The study was carried out on 692 responders and 223 non-responders. Results: After adjustment for gender, age at the RRT onset, RRT vintage, chronic glomerulonephritis as a cause of renal failure and mean serum parathyroid hormone level, VDR rs1544410 polymorphism was the only one significantly associated with response to hepatitis B vaccination: homozygotes AA (adjusted OR 1.50, 95% CI: 1.17–1.94, p = 0.002) had higher risk to be non-responders than GG homozygotes. Discussion: The VDR rs1544410 AA genotype may play a negative role (but not as an independent factor) in determining response to hepatitis B vaccination in RRT patients.

運動習慣と骨関連遺伝子多型が中高年者の超音波骨指標に及ぼす影響

The purpose of this study was to investigate the interaction of habitual exercise and candidate gene polymorphisms related to bone on osteo sono-assessment index (OSI) by quantitative ultrasound (QUS) in middle-aged and elderly Japanese. Participants were classified into exercise group (E; n=172, 62.3 ± 7.7 yr) and sedentary group (S; n=65, 58.6 ± 9.2 yr). The OSI was measured with AOS-100. DNA was extracted from blood, and single nucleotide polymorphism in vitamin D receptor, estrogen receptor α, and transforming growth factor-βI were genotyped by TaqMan assay. Group E had significantly lower body weight and body mass index (BMI) than Group S. In men, although Group E was older than Group S, Group E had significantly higher OSI rather than Group S. There was no significant interaction between habitual exercise and each gene polymorphism on OSI. These results essentially remained unchanged even when analysis of covariance was applied after adjustment for age, body weight, and BMI. These results suggest habitual exercise and genetic factors have no interaction on OSI in middle-aged and elderly Japanese. Further investigations are needed to prove the interaction of other gene polymorphisms and exercise.