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1.
Int J Environ Health Res ; : 1-10, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32281876

RESUMO

To assess the association between fluoride exposure and children's behavioural outcomes, we recruited 325 resident school-age children (7-13 years old) lived in Tongxu County of Henan Province in China. We measured urinary fluoride (UF) concentrations using the ion-selective electrode method. Children's behavioural outcomes were assessed by Conners' Parent Rating Scale-Revised, including conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive, anxiety, and ADHD index. It turned out that each 1.0 mg/L increment in UF concentration corresponded with an elevation in the psychosomatic problem score of 4.01 (95% CI: 2.74, 5.28) and a 97% (OR = 1.97, 95% CI: 1.19, 3.27) increase in the prevalence of psychosomatic problems after adjusting for potential influencing factors. The sensitivity analysis results were consistent with those observed in our preliminary analysis. Our study suggests that fluoride exposure is positively related to the behavioural problem in school-age children, psychosomatic problem in particular.

2.
Chemosphere ; 253: 126616, 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32283421

RESUMO

Excessive exposure to fluoride has been reported to affect bone mineral density (BMD). CALCA expression plays a critical part in bone formation. However, the role of CALCA in the association between fluoride and BMD is not known. We conducted a cross-sectional study and recruited 722 women in rural areas of Henan Province, China, to assess the relationship between fluoride exposure, CALCA methylation, and BMD. Urinary levels of fluoride, CALCA methylation, and BMD were measured by a fluoride ion-selective electrode, standalone ultrasound bone densitometer, and quantitative methylation-specific polymerases chain reaction, respectively. The association among fluoride exposure, CALCA methylation, and BMD was age-specific. Specifically, BMD was negatively correlated with methylation (ß: -0.008; 95% CI: -0.016, 0.000) and fluoride exposure (ß: -0.063; 95% CI: -0.129, -0.002) in women over 45 years and 50-54 years of age, respectively, whereas methylation was positively correlated with fluoride exposure (ß: 4.953; 95% CI: 1.162, 8.743) in women aged 40-44 years. Besides, increased BMD in women aged 45-49 years induced by the interactive effect of the highest methylation of CALCA exon 1 (tertile 3) and fluoride exposure was observed (P for interaction < 0.05). Our findings suggest an age-specific association between exposure to excessive fluoride, CALCA methylation, and BMD in a rural population of women in China. Notably, the susceptibility of BMD to fluoride exposure may be modified by CALCA methylation.

3.
Ecotoxicol Environ Saf ; 197: 110643, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32315786

RESUMO

Meteorological conditions during pregnancy can affect birth outcome, which has been linked to the H19/H19-differentially methylated region (DMR). However, the detailed mechanisms underlying this association are unclear. This was investigated in the present study to provide epidemiological evidence for elucidating the pathogenesis of adverse birth outcomes. A total of 550 mother-newborn pairs were recruited in Zhengzhou, China from January 2010 to January 2012. Meteorological data including temperature (T), relative humidity (RH), and sunshine duration (SSD) were obtained from the China Meteorological Data Sharing Service System. Bisulfite sequencing PCR was performed to determine the methylation levels of H19/H19-DMR using genomic DNA extracted from maternal peripheral and umbilical cord blood. The results showed that H19-DMR methylation status in cord blood was positively associated with that in maternal blood. Neonatal H19-DMR methylation was negatively associated with T and RH during the first trimester and positively associated with these variables during the third trimester. There was a positive correlation between neonatal H19-DMR methylation and SSD during the second trimester and a negative correlation during the third trimester. Similar associations were observed between maternal H19-DMR methylation and prenatal meteorological conditions. We also observed significant interaction effects of maternal H19/H19-DMR methylation and most prenatal meteorological factors on neonatal methylation, and found that changes in the methylation status of maternal H19-DMR were responsible for the effects of prenatal meteorological conditions on neonatal methylation. In summary, neonatal H19-DMR methylation was significantly associated with prenatal meteorological conditions, which was modified and mediated by maternal H19-DMR methylation changes. These findings provide insights into the relationship between meteorological factors during pregnancy and adverse birth outcomes or disease susceptibility in offspring, and can serve as a reference for environmental policy-making.

4.
Environ Toxicol ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167222

RESUMO

Glyburide is a classic antidiabetic drug that is dominant in inflammation regulation, but its specific role in ozone-induced lung inflammation and injury remains unclear. In order to investigate whether glyburide prevents ozone-induced pulmonary inflammation and its mechanism, C57BL/6 mice were intratracheally pre-instilled with glyburide or the vehicle 1 hour before ozone (1 ppm, 3 hours) or filtered air exposure. After 24 hours, the total inflammatory cells and total protein in bronchoalveolar lavage fluid (BALF) were detected. The pathological alternations in lung tissues were evaluated by HE staining. The expression of NLRP3, interleukin-1ß (IL-1ß), and IL-18 protein in lung tissues was detected by immunohistochemistry. Western blotting was used to examine the levels of caspase-1 p10 and active IL-1ß protein. Levels of IL-1ß and IL-18 in BALF were measured using ELISA kits. Glyburide treatment decreased the total cells in BALF, the inflammatory score, and the mean linear intercept induced by ozone in lung tissues. In addition, glyburide inhibited the expression of NLRP3, IL-18, and IL-1ß protein in lung tissues, and also suppressed NLRP3 inflammasome activation, including caspase-1 p10, active IL-1ß protein in lung tissues, IL-1ß, and IL-18 in BALF. These results demonstrate that glyburide effectively attenuates ozone-induced pulmonary inflammation and injury via blocking the NLRP3 inflammasome.

5.
Environ Toxicol Pharmacol ; 76: 103350, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32058320

RESUMO

Lead (Pb) is recognized as a potent inducer of synaptic toxicity generally associated with reduced synaptic transmission and increased neuronal fiber excitability, becoming an environmental risk for neurodegenerative processes. Despite numerous toxicological studies on Pb have been directed to the developing brain, attention concerning long-term consequences of pubertal chronic Pb exposure on neuronal activity is still lacking. Thus, we exposed 4-week-old male mice to 0.2 % lead acetate solution for one month, then, conducted behavioral tests or extracted brain homogenate from mice prefrontal cortex (PFC) and hippocampus at the age of 4, 13 and 16-month-old respectively. Our results showed that treated mice exhibited an evident increase in latency to reach platform following pubertal Pb exposure and aging. The increase of 8-OHdG revealed evident neural DNA oxidative damage across time upon pubertal Pb exposure. In the hippocampus of lead exposed mice at three age nodes, the expression of brain-derived neurotrophic factor precursor (proBDNF) increased, while that of mature BDNF (mBDNF), cAMP-response element binding protein (CREB) and phosphorylated CREB (pCREB) decreased compared with the control group. Furthermore, the expression of BACE1 protein and tau phosphorylation level in PFC and hippocampus increased, APP mRNAs in PFC and prolonged induction of BACE1 in hippocampus. Our results show that chronic Pb exposure from pubertal stage onward can either initiate divergent synaptic-related gene expression patterns in adulthood or trigger time-course of neurodegenerative profile within the PFC or hippocampus, which can contribute consistent deficits of cognition across subsequent age-nodes.

6.
Int J Environ Health Res ; 30(2): 174-186, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30810352

RESUMO

To assess heavy metal pollution and human health risk, a total of 28 topsoil samples were collected during four seasons from seven agricultural soil sites near a famous smelter in Jiyuan, China. The maximum concentrations of Cd, Pb, Hg, As, Zn, Cu, Ni, and Cr were 26.00, 2601.00, 3.29, 65.00, 410.00, 156.30, 54.80, and 73.60 mg kg-1, respectively. Compared with the sampling site nearest to the smelter, the concentrations of six metals at the farthest site were decreased significantly (P < 0.05). All sites were heavily contaminated, with Nemerow index (P) >3.0, and all sites had very high ecological risks related to Cd and Hg. The non-carcinogenic risk for children (based on combined exposure to the eight metals) was above the safety level. The carcinogenic risk of As for adults (8.98 × 10-6) and children (1.49 × 10-5) exceeded the acceptable level (1 × 10-6). Results suggest a serious health risk in the polluted areas, particularly for children.Abbreviation Cd: Cadmium; Pb: Lead; Hg: Mercury; As: Arsenic; Zn: Zinc; Cu: Copper; Ni: Nickel; Cr: Chromium; P: Nemerow index; RI: Potential ecological risk index; Ei: Monomial potential ecological risk of a specific heavy metal; HI: non-carcinogenic hazard index; CR: Carcinogenic risk; TN: Total nitrogen; TP: Total phosphorus; OM: Organic matter; MC: Moisture content; ADD: Average daily dose.

7.
J Hum Genet ; 65(3): 281-285, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31813936

RESUMO

Association between vitamin D receptor (VDR) genetic polymorphism and obesity was observed in several case-control studies. This study hypothesized that these associations could be verified in family-based study. We aimed at investigating the associations between VDR SNPs and obesity (BMI ≥ 28 kg/m2) by case-control study with 688 subjects and family-based study with 419 pedigrees. The results of case-control study suggested that rs3847987 (AC vs CC, Adjusted OR: 1.938, 95% CI: 1.359-2.763, P = 0.000405) was associated with obesity. Allele C of rs3847987 was risk factors for obesity (P = 0.006). Furthermore, association of rs3847987 with BMI was verified in family-based study (Z = 2.077, P = 0.037811). In addition, sibling with AC genotype of rs3847987 had significant higher BMI than CC genotype in the same family (P = 0.03). Therefore, it could be concluded that VDR genetic polymorphism (rs3847987) may be associated with obesity.

8.
Eur J Clin Nutr ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827258

RESUMO

BACKGROUND/OBJECTIVES: The present cross-sectional study evaluated the association of vitamin D receptor (VDR) variants with serum 25(OH)D3 levels and their interaction on essential hypertension (EH) risk. SUBJECTS/METHODS: 1539 patients were eligible in the study population. Two loci in VDR gene (rs2239179, rs2189480) were genotyped by TaqMan probe assays. Logistic regression, Kruskal-Wallis rank test and Chi-square test were used to determine the association among VDR polymorphisms, serum vitamin D metabolites, and the risk of EH. Interaction plots were performed to explain the interaction effects of circulating 25(OH)D3 levels and VDR variants on EH susceptibility. RESULTS: After potential confounding adjustment, we observed that the mutations of VDR (rs2239179/rs2189480) were associated with the increased risk of EH (P < 0.05). Moreover, plasma 25(OH)D3 levels were inversely associated with EH, However, we did not find the association between serum 25(OH)D3 and VDR variants. When comparing with wild-type homozygous and heterozygous genotype carriers with vitamin D sufficiency, hypovitaminosis D and insufficient participants carrying homozygous variant genotype of rs2239179 showed a higher risk of EH, increased by 113% (OR = 2.13, 95% CI: 1.20, 3.80); Notably, the detrimental effect of rs2239179 homozygous variant on EH became stronger in the case of serum 25(OH)D3 <30 ng/ml. However, we did not find the interaction effect between rs2189480 variants and serum 25(OH)D3 levels on the risk of EH. CONCLUSIONS: Our results suggested that the mutations of VDR may accelerate the progression of EH etiology, especially when suffering hypovitaminnosis D and insufficiency.

10.
Ecotoxicol Environ Saf ; 181: 428-434, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31220783

RESUMO

The evidence is increasing that prenatal air pollutant exposure contributes to elevated oxidative stress in children, but the underlying mechanism is unclear. A pilot study was conducted in China to explore the associations between prenatal ambient air pollution exposure and superoxide dismutase 2 (SOD2) promoter methylation in maternal and cord blood. After detection and analyses, SOD2 promoter methylation levels in umbilical cord blood were elevated as maternal SOD2 promoter methylation levels increased. In addition, the SOD2 promoter methylation levels in umbilical cord blood were positively associated with the particulate matter 10 (PM10) exposure concentrations during the entire pregnancy and the second trimester. In maternal peripheral blood, the SOD2 promoter methylation levels were positively associated with the exposure concentrations of PM10 (during the entire pregnancy and the second trimester) and nitrogen dioxide (NO2) (during the first trimester of pregnancy), whereas the levels were negatively associated with the exposure concentrations of NO2 during the third trimester of pregnancy. Additionally, interaction analyses revealed that the maternal SOD2 promoter methylation level and sulfur dioxide (SO2) exposure (during the entire pregnancy and the third trimester), as well as NO2 exposure (during the third trimester of pregnancy), had an interaction effect on the SOD2 promoter methylation level in umbilical cord blood. Furthermore, mediation analysis revealed that the associations between SOD2 promoter methylation in umbilical cord blood and PM10 exposure during the entire pregnancy and the second trimester were partly mediated by maternal SOD2 promoter methylation. In conclusion, prenatal exposure to air pollutants was significantly associated with SOD2 promoter methylation levels in umbilical cord blood, and this association may be affected by SOD2 promoter methylation levels in maternal peripheral blood. These associations may be one of the mechanisms by which prenatal air pollutant exposure leads to oxidative stress in newborns.


Assuntos
Poluição do Ar/análise , Metilação de DNA , Sangue Fetal/química , Exposição Materna , Superóxido Dismutase/genética , Poluentes Atmosféricos/sangue , China , Feminino , Humanos , Recém-Nascido , Masculino , Projetos Piloto , Gravidez , Regiões Promotoras Genéticas , Fatores de Risco , Superóxido Dismutase/sangue
11.
Lipids Health Dis ; 18(1): 97, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975133

RESUMO

BACKGROUND: Evidence shows that low serum vitamin D concentrations account for an increased risk of obesity by inducing vitamin D receptor (VDR) hypofunction. Although the correlation between single nucleotide polymorphisms (SNPs) of VDR gene and obesity-related anthropometric measures (such as body mass index [BMI] and waist circumference[WC]) has already been tested, there are only few studies on the association between direct measures of body fat percentage (BFP) and triceps skinfold thickness and the SNPs of VDR. The aim of the present study was to evaluate the effect of VDR gene polymorphism on multiple obesity indexes in Han Chinese, including BMI, WC, BFP and triceps skinfold thickness. METHODS: In this cross-sectional study, five hundred and seventeen healthy Chinese adults were enrolled in the trial. Four loci in VDR gene (rs2228570 [FokI], rs2189480, rs2239179 and rs7975232[ApaI]) were genotyped by TaqMan probe assays. Obesity indexes including BMI, WC, BFP and triceps skinfold thickness were used to evaluate the relationship to the VDR SNPs. Multiple logistic regression, linear regression and general multifactor dimensionality reduction (GMDR) were performed to analyze the correlation of VDR gene and obesity indexes. RESULTS: None of the VDR SNPs were associated with BMI and WC, the C allele of FokI and the T allele of ApaI were associated with an increase in BFP (ß = 0.069,P = 0.007; ß = 0.087, P = 0.022 respectively); the G allele of rs2239179 and the T allele of ApaI were associated with an increase in triceps skin fold thickness (ß = 0.074, P = 0.001; ß = 0.122, P < 0.001 respectively). In regards to adiposity-related metabolic parameters, we found that the GT genotype of ApaI was associated with higher level of total cholesterol (TC) (P = 0.013) and Low-density lipoprotein cholesterol (LDL-C) (P = 0.001). CONCLUSIONS: Though we failed to prove that VDR SNPs were in correlation with BMI and WC, we did establish the association between VDR variants and BFP, as well as triceps skinfold thickness. Data obtained suggested that the VDR variants play an important role in regulating adipose tissue activity and adiposity among Han Chinese.


Assuntos
Tecido Adiposo/metabolismo , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Pregas Cutâneas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Índice de Massa Corporal , China/epidemiologia , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Expressão Gênica , Loci Gênicos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redução Dimensional com Múltiplos Fatores , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/epidemiologia , Receptores de Calcitriol/sangue , Circunferência da Cintura
12.
Ecotoxicol Environ Saf ; 172: 40-44, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30677743

RESUMO

A number of epidemiological studies have reported that chronic exposure to high concentrations of fluoride not only causes dental and skeletal fluorosis but additionally affects serum levels of reproductive hormones. However, possible interaction between fluoride exposure and estrogen receptor alpha (ESRα) gene polymorphisms on sex hormone-binding globulin (SHBG) and androgen binding protein (ABP) of male farmers has not been detailed. Here, we conducted a cross-sectional study including 348 male farmers with different fluoride exposure levels from drinking water in Henan province of China to explore effects of fluoride exposure and ESRα genetic variation on serum SHBG and ABP levels. We found serum SHBG levels in male farmers from the high exposure group to be lower than those of the low exposure group. We also found that concentrations of SHBG affected ABP levels. Furthermore, fluoride exposure and single nucleotide polymorphisms at the XbaI and rs3798577 loci of the ESRα gene affected serum ABP levels. Our findings suggest that chronic fluoride exposure from drinking water is associated with alterations of serum SHBG and ABP concentrations in local male farmers and that the effect of fluoride exposure on ABP levels vary depending on ESRα gene polymorphisms.


Assuntos
Proteína de Ligação a Androgênios/sangue , Água Potável/química , Receptor alfa de Estrogênio/genética , Fazendeiros , Fluoretos/toxicidade , Globulina de Ligação a Hormônio Sexual/metabolismo , China , Estudos Transversais , Exposição Ambiental/análise , Feminino , Fluoretos/metabolismo , Fluoretos/urina , Interação Gene-Ambiente , Genótipo , Hormônios , Humanos , Modelos Lineares , Masculino , Análise Multivariada , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único
13.
Reprod Toxicol ; 84: 98-107, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30633982

RESUMO

We previously investigated excessive fluoride exposure elicited intracellular endoplasmic reticulum (ER) stress and led to Sertoli cells dysfunction in vitro. However, the mechanisms underlying fluoride-mediated male reproductive damage in vivo remain largely unknown. Considerable evidence has now revealed ER stress is closely linked with testicular oxidative damage. Hence, we aimed to explore whether ER stress signaling was involved in the testicular protective effects of antioxidant N-acetylcysteine (NAC) against testicular apoptosis induced by fluoride. Male SD rats were oral gavaged with sodium fluoride (NaF) for 7 weeks to induce fluorosis. The animals were pretreatment with or without NAC (150 mg/Bw•d). Our results demonstrated that sub-chronic NaF exposure triggered testicular apoptosis and sex hormonal disturbance in pituitary-testicular (PT) axis, promoted oxidative stress and the expression of ER stress mediators. Antioxidant NAC, however, prevented NaF-induced testicular apoptosis accompanied by activating Nrf2-mediated antioxidant potential. Simultaneously, NAC pretreatment downregulated XBP1 splicing, reduced JNK phosphorylation and further blocked cleavage of caspase-3, all these might contribute to the inhibition of testicular cell apoptosis. Collectively, the present results suggested that prolonged administration of NAC preserved testicular function and normalized sex hormonal disruption induced by NaF via the inhibition of Nrf2-associated oxidative damage and Ire1α-JNK-mediated apoptosis in rat testis.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Fluoretos/toxicidade , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Endorribonucleases/genética , Endorribonucleases/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Testículo/metabolismo
15.
Environ Toxicol Pharmacol ; 66: 14-23, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30593950

RESUMO

Both ß-amyloid (Aß) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aß degradation enzymes in Pb-induced latent effects on Aß overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aß1-42 and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aß accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aß accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aß clearance.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Chumbo/toxicidade , Linhagem Celular , Epigênese Genética , Inibidores de Histona Desacetilases/farmacologia , Histonas/metabolismo , Humanos , Insulisina/genética , Insulisina/metabolismo , Neprilisina/genética , Neprilisina/metabolismo , Tretinoína/farmacologia , Ácido Valproico/farmacologia
16.
Chemosphere ; 212: 863-871, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30193235

RESUMO

Prenatal exposure to air pollutants is believed to be associated with adverse birth outcomes. However, the potential mechanisms, especially the epigenetic modified effects, still remain unclear. This study was designed to explore the association of air pollution, H19/DMR methylation levels, and birth weight and length. A total of 527 mother-infant pairs were recruited from Houzhai Center Hospital, Zhengzhou. Air pollution data during the study period was collected. The methylation at H19 promoter region and H19 DMR in maternal and cord bloods were determined using real-time PCR analysis. Ridge regression was used to analyze the association of air pollutants exposure during gestation with H19/DMR methylation and birth weight and length respectively. Results showed that prenatal exposure to NO2 was associated with higher H19 methylation in cord blood. Whereas SO2 and PM10 exposure were associated with lower H19 and H19 DMR methylation respectively. After stratification by pregnancy trimesters, the association of H19 methylation in cord blood with PM10 exposure also was found. Furthermore, prenatal exposures to air pollutants also were associated with birth weight and length. Specifically, with the increase of maternal SO2 exposure during the entire pregnancy, birth weight and length significantly decreased. While birth weight and birth length were significantly increased with NO2 exposure. The stratified analysis also found the associations between PM10 exposure and birth sizes in different trimesters. In conclusion, the gene methylation level in cord blood might be associated with prenatal environmental exposures. Birth weight and length were associated with both prenatal environmental exposures and genetic factors.


Assuntos
Peso ao Nascer , Exposição Ambiental/efeitos adversos , Sangue Fetal/química , Recém-Nascido , Exposição Materna/efeitos adversos , Gravidez , RNA Longo não Codificante/metabolismo , Adulto , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/farmacologia , Poluição do Ar/análise , China , Exposição Ambiental/análise , Feminino , Humanos , Lactente , Masculino , Metilação , Dióxido de Nitrogênio/efeitos adversos , Projetos Piloto
17.
Gene ; 678: 172-176, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30081191

RESUMO

BACKGROUND: A low serum vitamin D concentration is associated with an increased risk of type 2 diabetes mellitus (T2DM). Recently, several single nucleotid polymorphisms (SNPs) have been identified which influence vitamin D levels. If a causal relationship exists between vitamin D concentrations and T2DM, one would expect a similar association between the newly identified SNPs and T2DM risk. Therefore, this study investigated the association between four SNPs of cytochrome P450 family 2, subfamily R, peptide 1 (CYP2R1) gene, serum 25(OH)D3 levels and T2DM. METHODS: Three hundred and ninety-seven patients with confirmed T2DM, as well as 397 age- and gender-matched controls were enrolled in this case-control study. Genotyping was performed by TaqMan probe assays. Kruskal-Wallis one-way analysis and muitiple logistic regression analysis were performed to identify the possible risk genotype for vitamin D levels and T2DM, respectively. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-environment interactions. RESULTS: The serum 25(OH)D3 levels were significant lower in the T2DM group. Significant differences were observed between patients and controls in terms of the genotype distributions of rs1993116 (P = 0.048) and rs10766197 (P = 0.024). Similarly, rs1993116 and rs10766197 polymorphisms were found to be significantly associated with T2DM risk. AG + GG genotype carriers of the rs1993116 and rs10766197 polymorphisms could have an increased risk of developing T2DM compared with AA carriers, the OR and 95% CI were 1.64 (1.09-2.46) and 1.76 (1.18-2.65), respectively. However, none of the tested SNPs were independently associated with serum 25(OH)D3 levels (P > 0.059). Gene-gene and gene-environment interaction analyses indicated that rs12794714-rs10766197 and rs12794714-vitamin D deficiency (VDD) models successfully predicted T2DM risk (P < 0.001). CONCLUSIONS: Rs1993116 and rs10766197 polymorphisms of CYP2R1 gene may be novel genetic markers for T2DM in China. Given the lack of association between SNPs and serum 25(OH)D3 levels, well-designed future studies should be conducted with larger sample sizes in rural areas of China.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Calcifediol/sangue , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Diabetes Mellitus Tipo 2/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , População Rural
18.
Nutr Res ; 54: 52-59, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29914667

RESUMO

As the major vitamin D binding protein (DBP), the group-specific component (GC) plays an important role in the bioactivity of vitamin D. Abnormal expression of GC gene may be associated with vitamin D related disease, type 2 diabetes mellitus (T2DM). DNA methylation is an important regulator of gene expression. It has been reported that methylation in 3' untranslated region played a role in regulation of protein expression via interaction with miRNA. This study hypothesized that DNA methylation of 3' near region of GC gene (3'GC) might be associated with T2DM. The methylation status of the 3'GC was assessed with high resolution melt method. Logistic regression was applied to assess the risk of T2DM at different levels of 3'GC methylation. The results showed that methylation level of the 3'GC was higher in T2DM patients than in non-T2DM individuals (P=.038). There was a significant association between 3'GC methylation level and T2DM (adjusted OR 1.282; 95% CI 1.062-1.548; P=.01). The association was independent upon serum glucose and insulin (adjusted OR 1.561; 95% CI 1.083-2.249; P=.017). Furthermore, there was a positive correlation between methylation level and the level of DBP in T2DM patients (r=0.126, P=.036). The association was also significant after adjusting the potential impact of rs705117 (P=.044). Besides, a positive correlation between methylation level and the level of fasting serum insulin was observed in non-T2DM (r=0.101, P<.001). These results suggest that methylation status of the 3'GC is most likely associated with DBP expression, insulin secretion, and T2DM.


Assuntos
Metilação de DNA , Diabetes Mellitus Tipo 2/metabolismo , Insulina/sangue , Proteína de Ligação a Vitamina D/metabolismo , Vitamina D/sangue , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Epigênese Genética , Feminino , Regulação da Expressão Gênica , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances
19.
J Diabetes Complications ; 32(4): 406-410, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29428204

RESUMO

AIMS: Association between T2DM and vitamin D was found in many epidemiologic reports. And 24-hydroxylase encoded by CYP24A1 is the very enzyme that degrades the active vitamin D metabolite. We aimed to investigate the association between rs4809957 in CYP24A1 and T2DM, as well as vitamin D level. METHODS: A total of 419 pedigrees containing 1556 participants were included. T2DM diagnosis, 25(OH)D measurement and genotyping of rs4809957 were conducted for all the individual. Then association between rs4809957 and T2DM, as well as 25(OH)D level, was investigated by family-based association test (FBAT) and 1:1 matched case-control study. RESULTS: The FBAT results revealed that there was transmission disequilibrium for allele G in T2DM families by both additive model (Z = 2.183, P = 0.029049) and recessive model (Z = 2.236, P = 0.025347). Allele G was also associated with 25(OH)D level in both additive model (Z = 2.549, P = 0.010811) and dominant model (Z = 2.012, P = 0.044187). On the other hand, results of case-control study suggested that vitamin D deficiency was a risk factor for T2DM (OR 1.987; 95%CI 1.331-2.964; P = 0.001). Further stratified analysis revealed that vitamin D deficiency increased T2DM risk in women (OR 2.347; 95%CI 1.373-4.012; P = 0.002), instead of men (OR 1.600; 95%CI 0.874-2.931; P = 0.127). In addition, T2DM patients with GG and AG genotypes were more susceptible to vitamin D deficiency than the control (P = 0.006 and P = 0.038, respectively). CONCLUSION: There was transmission disequilibrium for allele G of rs4809957 in T2DM families, which was linked to vitamin D deficiency.


Assuntos
Diabetes Mellitus Tipo 2/genética , Deficiência de Vitamina D/genética , Vitamina D3 24-Hidroxilase/genética , Vitamina D/análogos & derivados , Alelos , Estudos de Casos e Controles , Família , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Linhagem , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Vitamina D/genética
20.
Sci Rep ; 8(1): 1345, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29358755

RESUMO

Association between T2DM and vitamin D deficiency has been reported in many epidemiologic studies. 24-hydroxylase encoded by CYP24A1 is the enzyme that degrades the active vitamin D metabolite. Variation in CYP24A1 may be associated with T2DM. This study investigates the association between rs2248359 in CYP24A1 and T2DM by a family-based association test (FBAT) and in a case-control study. The FBAT results revealed that there was transmission disequilibrium for allele T in both additive model (Z = 2.041, P = 0.041227) and dominant model (Z = 2.722, P = 0.006496). Results of the case-control study suggested that rs2248359 may be a risk factor for female T2DM (P = 0.036) but not for male T2DM (P = 0.816). Furthermore, excessive transmission of allele T in T2DM offspring was observed compared with the non-T2DM offspring (OR 1.392; 95%CI 1.024-1.894; P = 0.035). In addition, combination of maternal CT and paternal CC genotypes had significant synergistic effect on obtaining CT genotype for offspring with T2DM (OR 6.245; 95%CI 1.868-20.883; P = 0.004). Besides, lower level of 25(OH)D in T2DM offspring with genotype CT was observed as compared with the non-T2DM offspring (P = 0.013). These data suggest that maternal transmission disequilibrium of allele T may be a risk factor for T2DM and vitamin D deficiency in T2DM offspring.


Assuntos
Diabetes Mellitus Tipo 2/genética , Herança Materna , Polimorfismo de Nucleotídeo Único , Deficiência de Vitamina D/complicações , Vitamina D3 24-Hidroxilase/genética , Alelos , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Linhagem , Fatores Sexuais , Deficiência de Vitamina D/genética
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