Obesity-related genetic polymorphisms are associated with the risk of early puberty in Han Chinese girls.

OBJECTIVE: To explore the association between obesity and precocious puberty from the perspective of genetic polymorphism. DESIGN: Two hundred and ninety-eight pairs of girls in early puberty and age-matched controls (±3 months) were recruited. The genotypes of four obesity-related single-nucleotide polymorphism (SNP) loci (rs10968576, rs12935153, rs4674340 and rs7635103) were determined and the effect of variation on early puberty in Chinese Han girls was evaluated. The unstimulated luteinizing hormone (LH), follicle-stimulating hormone and estradiol levels were also measured to determine the relationship with SNP polymorphisms. RESULTS: The effect allele A of rs12935153 was associated with early puberty (odds ratio [OR] = 1.256, 95% confidence interval [CI]: 1.010-1.585), but the significance disappeared after multiple comparisons. After adjusting for body mass index, rs12935153 variation increased the risk of early puberty in additive (OR = 1.589, 95% CI: 1.222-2.066), dominant (OR = 1.788, 95% CI: 1.210-2.642) and recessive (OR = 1.915, 95% CI: 1.207-3.038) models of inheritance. Individuals harbouring AA genotype in rs12935153 had a risk of higher LH levels than that of wild type (OR = 1.668, 95% CI: 1.093-2.546). CONCLUSIONS: The association between obesity and precocity can be explained from a genetic perspective. Our study suggests that variations in rs12935153 increase the risk of early puberty in Chinese girls. Further studies are needed to verify our findings.

Urinary phthalate metabolites in primary school starters in Pearl River Delta, China: Occurrences, risks and possible sources.

Assessment of children's exposure risks of phthalates before puberty is important, as phthalates are ubiquitous and are associated with reproductive development. However, relevant data in Pearl River Delta, China are scarce. Nineteen phthalate metabolites were analyzed in urine samples from 1490 primary school starters (6-8 years old) recruited in 2016-2017 using ultra-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS). Nine phthalate metabolites were detected more than 80% of the urine samples. Monobutyl phthalate (MnBP) was the highest metabolite (median, 212 µg/g creatinine), followed by two short chained phthalate metabolites, four secondary metabolites of di(2-ethylhexyl) phthalate (DEHP), and the primary metabolites of DEHP. The MnBP level was the third highest of those reported worldwide while other metabolites were in the lower range compared with previous studies. Significantly positive associations were found between urinary metabolite levels and family income as well as parent education levels (p < 0.05). Duration since the latest interior decoration was inversely associated with phthalate metabolites (p < 0.05). Significantly positive associations had also been found between the frequency of eating takeaway food and four DEHP metabolites (p < 0.01). The geometric mean of estimated daily intake (EDI) of di-n-butyl phthalate (DnBP), DEHP, di-iso-butyl phthalate (DiBP), dimethyl phthalate, diethyl phthalate and butylbenzyl phthalate (BBzP) were 6.24, 2.67, 1.06, 0.64, 0.44, and 0.01 µg/kg bw/day, respectively. Hazard quotient (HQ) was defined as the ratio of EDI and the tolerable daily intake (TDI). Approximately 38% children had HQ DnBP >1 indicating potential reproductive risks caused by DnBP. To evaluate cumulative exposure risks, hazard index (HI) was calculated as the sum of the HQs of DnBP, DiBP, DEHP, and BBzP. Nearly 48% children had HI > 1 suggesting extremely high cumulative risks in children in Pearl River Delta, China. To our best knowledge, this was the largest study on evaluating phthalate exposure among children in China.

Prevalence of dental caries and its association with body mass index among school-age children in Shenzhen, China.

BACKGROUND: Dental caries and overweight/obesity are health problems with shared risk factors, but the relationships between caries and BMI need to be further explored. The objective was to evaluate the current status of dental caries and the association between dental caries and Body Mass Index (BMI) among primary and secondary school students in Shenzhen, China, during the 2016-2017 academic year. METHODS: A population-based, cross-sectional study that enrolled a total of 1,196,004 students was conducted in Shenzhen. Physical and dental examinations were given to all primary and secondary school students by certified physicians and dentists following the national specification for student health examinations, and dental caries was diagnosed using WHO criteria. Descriptive analysis was applied to assess current oral health status and a multifactorial, logistic regression model was employed to evaluate the relationship between dental caries and obesity. RESULTS: A total of 1,196,004 students participated in the census. Mean age of the participants was 10.3 years, ranging from 6 to 20 years. The prevalence of dental caries was 41.15% in the present study, which was higher among girls (42.88%) than that in boys (39.77%) with a p-value of < 0.001. Students in public schools showed a significantly lower (p < 0.001) caries prevalence (37.36%) compared with those in private schools (47.96%). The caries restoration rate of students in Shenzhen was only 10.30%, which means only one out of ten students with caries received restorations. The mean dmft and DMFT scores were 0.97 and 0.33, respectively. More girls (10.96%) had their teeth filled than boys (9.78%). The restoration rate was higher (p < 0.001) in public schools (11.73%) than in private ones (8.35%). Children who were overweight or obese had a lower risk of experiencing caries compared to those who were within a normal weight (OR = 0.74/0.64). Caries was inversely associated with BMI among primary and secondary school students in Shenzhen. CONCLUSIONS: The prevalence of dental caries among primary and secondary school children was found to be related to sex, type of schools, region, and BMI. Further studies and more government support are required to confirm the findings of this study and to address current oral health problems.

Characteristics and related factors of nonfatal injuries among adolescents and college students in Shenzhen City of China.

BACKGROUND: Injuries impact adolescents and young adults in unique ways. The purpose of this study was to determine the incidence rate of nonfatal injuries, and identify characteristics and risk factors for the injuries among adolescents and college students in Shenzhen, China. METHODS: A total of 4,138 students from 79 classes were selected using a purposive sampling method in 2010. The questionnaire included personal demographics, behavioral factors, and self-perceived agrypnia. Stepwise multivariate logistic regression models were used to explore the risk factors of injury. RESULTS: The annual incidence rate of nonfatal injuries was 13.5%. Injuries were significantly correlated with gender (boys vs. girls, adjusted odds ratio [OR], 1.58, 95% confidence interval [CI], 1.30-1.93) and self-perceived agrypnia (sometimes vs. no, adjusted OR, 1.64, 95% CI, 1.31-2.05; often vs. no, adjusted OR, 2.34, 95% CI, 1.74-3.14), attending PE class ( >2 classes/week vs. ≤ 2 classes/week, adjusted OR, 1.25, 95% CI, 1.04-1.51), sexual behaviors (yes vs. no, adjusted OR, 1.46, 95% CI, 1.03-2.07), physical fighting (yes vs. no, adjusted OR, 1.84, 95% CI, 1.49-2.28), alcohol consumption (yes vs. no, adjusted OR, 1.29, 95% CI, 1.06-1.59), unsafe cycling (yes vs. no, adjusted OR, 1.47, 95% CI, 1.20-1.80) and skating in unsafe places (yes vs. no, adjusted OR, 1.57, 95% CI, 1.10-2.24). Additionally, falls were the leading cause of injuries, and gymnasiums of schools were the most-reported places where injuries occurred. CONCLUSIONS: Nonfatal injuries have turned into a pressing public health problem among adolescents and college students in Shenzhen, China. Strategies targeting the risk factors may be effective for the prevention of injuries.

Phthalates, physical activity, and diet, which are the most strongly associated with obesity? A case-control study of Chinese children.

PURPOSE: Phthalate esters have been a research hotspot recently owing to potential obesogenic activity, but conflicting results have been reported. This case-control study was designed to investigate whether there was an association between phthalate metabolites and childhood obesity in China. METHODS: A total of 240 pairs of obese/overweight children and age- (±3 months) and gender-matched controls were recruited. Nine phthalate metabolites were analyzed in the first morning urine sample. Physical activity and dietary intake were recorded using validated questionnaires. RESULTS: In monofactor analysis, the levels of monomethyl phthalate (MMP) and monobutyl phthalate (MnBP) in controls were significantly higher than those of overweight/obese children (p < 0.05). Moderate physical activity (p = 0.004), consumption of vegetables, fruits, and tonic were significantly higher in controls (all p < 0.05), and consumption of fried food, western fast food, carbonated drinks, and juice were higher in cases (all p < 0.05). After adjusting for physical activity and dietary intake, neither MMP [OR = 0.825, (95% CI: 0.559-1.217)] nor MnBP [(OR = 0.808, 95% CI: 0.556-1.176)], were significantly associated with obesity. In all models, moderate physical activity was negatively associated and high glucose high fat dietary patterns were positively associated with the risk of childhood obesity (p < 0.01). CONCLUSION: Diet and physical activity, but not phthalate metabolites were associated with childhood obesity. Further studies are needed to verify our findings. The trial was registered at clinicaltrials.gov as NCT05622513.

Neurotransmitter-precursor-supplement intervention for detoxified heroin addicts.

This study examined the effects of combined administration of tyrosine, lecithin, L-glutamine and L-5-hydroxytryptophan (5-HTP) on heroin withdrawal syndromes and mental symptoms in detoxified heroin addicts. In the cluster-randomized placebo-controlled trial, 83 detoxified heroin addicts were recruited from a detoxification treatment center in Wuhan, China. Patients in the intervention group (n=41) were given the combined treatment with tyrosine, lecithin, L-glutamine and 5-HTP and those in the control group (n=42) were administered the placebo. The sleep status and the withdrawal symptoms were observed daily throughout the study, and the mood states were monitored pre- and post-intervention. The results showed that the insomnia and withdrawal scores were significantly improved over time in participants in the intervention group as compared with those in the control group. A greater reduction in tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia and total mood disturbance, and a greater increase in their vigor-activity symptoms were found at day 6 in the intervention group than in the control group (all P<0.05). It was concluded that the neurotransmitter-precursor-supplement intervention is effective in alleviating the withdrawal and mood symptoms and it may become a supplementary method for patients' recovery from heroin addiction.

Association between polymorphisms of DRD2 and DRD4 and opioid dependence: evidence from the current studies.

Several studies have assessed the association between genetic polymorphisms of DRD2 and DRD4 genes and opioid dependence risk, while the results were inconsistent. We performed a meta-analysis, including 6,846 opioid dependence cases and 4,187 controls from 22 individual studies, to evaluate the roles of four variants (DRD2 -141ins/delC, rs1799732; DRD2 311 Ser > Cys, rs1801028; DRD2-related TaqI A, rs1800497 and DRD4 exon III VNTR) in opioid dependence for the first time. We found that the -141delC polymorphism was significantly associated with increased risk of opioid dependence (homozygote comparison: odds ratios [OR], 2.71; 95% confidence interval [CI], 1.74-4.22; dominant comparison: OR, 1.27; 95% CI, 1.09-1.48). Similarly, the TaqI A1 polymorphism was also significantly increased opioid dependence risk (homozygote comparison: OR, 2.06; 95% CI, 1.25-3.42; dominant comparison: OR, 1.34; 95% CI, 1.08-1.67). Moreover, long allele (≥5-repeat) and 7-repeat allele of DRD4 exon III VNTR were found to be associated with significantly increased opioid dependence risk (OR, 1.50; 95% CI, 1.24-1.80 and OR, 1.57; 95%, 1.18-2.09, respectively). However, no association was detected between the DRD2 311 Ser > Cys polymorphism and opioid dependence. In conclusion, our results suggested that DRD2 -141ins/delC, DRD2-related TaqI A and DRD4 exon III VNTR polymorphisms might play important roles in the development of opioid dependence.

The relationship between problem behavior and neurotransmitter deficiency in adolescents.

This study examined the association of problem behavior with neurotransmitter deficiency in adolescents, which would provide new insights into behavioral problems. A total of 1259 students of the seventh grade from 4 middle schools in Wuhan city located in the central China were recruited. With the approval of school and parents, they were invited to complete the Youth Self-Report (YSR) questionnaire and Symptom Scale of Neurotransmitter Deficiency (SSND) questionnaire. Pearson's bivariate correlation analysis showed that the correlation coefficients between each subscale of YSR and SSND ranged from 0.24 to 0.61 with all P<0.01. Canonical correlation analysis indicated that anxiety/depression was interrelated with insufficiency of GABA and 5-HT; aggressive behavior was associated with inadequate GABA; famine of DA influenced the attention problems. It was concluded that neurotransmitter deficiency may cause a series of behavioral and mental problems.

Association of Polymorphisms in the Kisspeptin/GPR54 Pathway Genes With Risk of Early Puberty in Chinese Girls.

CONTEXT AND OBJECTIVE: This case control study was designed to investigate the association between mutation of 10 single nucleotide polymorphism (SNP) loci (rs1132506, rs5780218, rs192636495, rs4889, rs184749, rs12985070, rs708910, rs932491, rs8074995, and rs2306877) in all 5 genes (KISS1, GPR54, PLCB1, PRKCA, and ITPR1) in the kisspeptin/GPR54 pathway and the risk of early puberty in Chinese Han girls. DESIGN AND PARTICIPANTS: A total of 314 pairs of early puberty girls on their first visit to hospital and age-matched controls (± 3 months) were recruited. The genotypes of each SNP were determined and the effect of loci variation on early puberty was investigated. RESULTS: rs5780218 was significantly associated with early puberty in additive, dominant, and recessive models of inheritance after adjusting for confounding factors (Pr < .05). After stratification, rs5780218 variation (odds ratio [OR], 1.650, 95% confidence interval [CI], 1.155-2.355 in additive models and OR, 2.116; 95% CI, 1.187-3.770 in recessive models) increased the risk of central precocious puberty (CPP); mutation in rs708910 (OR, 2.768; 95% CI, 1.305-5.872 in recessive model) had a positive association with the risk of CPP; and rs932491 variation was negatively associated with early and fast puberty (EFP) (OR, 0.309; 95% CI, 0.144-0.661 in additive models and OR, 0.317; 95% CI, 0.141-0.713 in dominant models). CONCLUSIONS: Our study suggests that mutation in rs5780218 and rs708910 increases the risk of CPP. rs932491 variation may have a protective effect on the risk of EFP. Further studies in larger populations or with people from different regions are needed to verify our findings.

Phthalate exposure linked to high blood pressure in Chinese children.

BACKGROUND: Exposure to phthalate esters may be linked to the risk of high blood pressure (HBP), but limited evidence is available in Chinese children. OBJECTIVE: To investigate the associations between nine phthalate metabolites (mPAEs) and systolic/diastolic BP, pulse pressure (PP), mean arterial pressure (MAP), and the risk of HBP. METHODS: In this cross-sectional study, a total of 1044 primary school children (6-8 years old) were enrolled from Shenzhen, China, between 2016 and 2017. Nine mPAEs were analyzed from urine using ultra-performance liquid chromatography and tandem mass spectrometry. A multivariable linear regression model was used to explore the associations between phthalate exposure and systolic/diastolic BP, PP, and MAP. A binary logistic regression model was used to examine the associations between phthalate exposure and the risk of HBP. RESULTS: Monomethyl phthalate (MMP) concentrations were significantly higher in HBP children than normal BP children. MMP, monoisobutyl phthalate (MiBP), monobutyl phthalate (MnBP), mono(5-carboxy-2-ethylpentyl) phthalate, mono-[(2-carboxy methyl)hexyl] phthalate (MCMHP), the sum of four short-chain mPAEs (∑LMW), and the sum of all nine mPAEs (∑9mPAEs) were significantly positively associated with increases in systolic BP z-score, while only MMP was significantly positively associated with diastolic BP z-score. MMP, MiBP, MnBP, MCMHP, ∑LMW, and ∑9mPAEs were significantly associated with increases in PP, while MMP and MnBP were significantly associated with increases in MAP. MMP was significantly associated with the risk of HBP, with an odds ratio of 1.87 (95% CI: 1.23, 2.85). CONCLUSIONS: The present study suggests that dimethyl phthalate exposure increases the risk of HBP. And some types of phthalates are associated with elevations in systolic/diastolic BP z scores, PP, and MAP in Chinese children.

Phthalates in PM2.5 from Shenzhen, China and human exposure assessment factored their bioaccessibility in lung.

Temporal variability of phthalates (PAEs) in PM2.5 from Shenzhen during 2015-2016 was measured and the associated human exposure via inhalation was assessed. The PM2.5 concentrations ranged from 30.7 to 115 µg m-3, greater than the air quality guidelines of interim target-3 (10-15 µg m-3) and interim target-2 (15-25 µg m-3) set by World Health Organization. PAEs were detected in 94.7% samples and the 95th percentile concentrations of total PAEs (∑6PAEs) in Longgang and Nanshan districts were 324 and 44.7 ng m-3, respectively. Di-2-ethylhexyl phthalate was the dominant species, accounting for an average of 81.9% of ∑6PAEs. The mean and 95th percentile concentrations of ∑6PAEs in PM2.5 were used to calculate a "typical" and "high" total daily intake and uptake, respectively. The estimated total daily intakes of PAEs varied and depended on body weight in each age group. Infants had the highest "typical" and "high" daily intake of 43.4 and 179 ng kg-body weight (bw) -1 day-1 for boys, and 42.0 and 173 ng kg-bw-1 day-1 for girls, respectively. However, after taking the bioaccessibility of PAEs in PM2.5 into account, the total daily "typical" and "high" uptakes dropped to 27.3 and 113 ng kg-bw-1 day-1 for male infants, and 29.0 and 120 ng kg-bw-1 day-1 for female infants, respectively. Both of the data on the daily "high" intake and uptake were much lower than the tolerable daily intake set by the European Food Safety Agency. It merits attention that infants were subject to greater PAE exposure than adults.

Urinary bisphenol analogues and triclosan in children from south China and implications for human exposure.

Bisphenols and triclosan (TCS) are widely used in consumer products. However, knowledge on human exposure to these anthropogenic chemicals has remained limited in China, especially for children. In this study, concentrations of seven bisphenols and TCS were determined in 283 urine samples collected from South China children aged between 3 and 11 years old. Bisphenol A (BPA), bisphenol S (BPS) and TCS were frequently detected in urine samples, with a detection rate of 93%, 89%, and 95%, respectively. Urinary concentrations of Σ7BPs (the sum concentrations of the seven bisphenols) ranged from 0.43 to 31.5 µg/L, with a median value of 0.91 µg/L, while TCS concentrations ranged from < limit of quantification to 21.9 µg/L (median: 0.21 µg/L). BPA was the predominant analogue (median: 0.35 µg/L), accounting for 49.8% of Σ7BPs. The urinary BPA concentrations in children from Guangzhou were significantly greater than those from Shenzhen. Correlation analysis suggested that multiple exposure sources to South China children likely existed for BPA, BPS, and TCS. Age, but not gender, was negatively associated with urinary residues of BPA and BPS (p < 0.05) and positively with TCS concentrations (p < 0.05). The estimated daily intake of Σ7BPs (23.9 ng/kg bw/day) or TCS (5.63 ng/kg bw/day) was below the tolerant reference dose of BPA, indicating no considerable health hazard to South China children.

Urinary metabolites of organophosphate esters in children in South China: Concentrations, profiles and estimated daily intake.

Organophosphate esters (OPEs) are widely used in household products as flame retardants or plasticizers and have become ubiquitous pollutants in environmental media. However, little is known about OPE metabolites in humans, especially in children. In this study, eight OPE metabolites were measured in 411 urine samples collected from 6 to 14-year-old children in South China. Bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP) and diphenyl phosphate (DPHP) were the dominant OPE metabolites, and their median concentrations were 1.04, 0.15 and 0.28 µg/L, respectively. The levels of urinary OPE metabolites in the present study were much lower than those in participants from other countries, with the exception of BCEP, suggesting widespread exposure to tris(2-chlorethyl) phosphate (TCEP, the parent chemical of BCEP) in South China. No significant difference in the concentrations of any of the OPE metabolites was observed between males and females (p > .05). Significant negative correlations were observed between age and BCEP, BCIPP, bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-o-cresyl phosphate (DoCP) and di-p-cresyl phosphate (DpCP) (DCP), or DPHP (p < .05). Pearson correlation coefficients between urinary OPE metabolites indicated multiple sources and OPE exposure pathways in children. The estimated daily intake suggested that children in South China have a relatively high exposure level to TCEP. To the best of our knowledge, this is the first study to report the urinary levels of OPE metabolites in Chinese children.

Nonfatal work-related injuries among agricultural machinery operators in northern China: a cross-sectional study.

PURPOSE: To identify the annual prevalence and potential risk factors of nonfatal agricultural machinery injuries among agricultural machinery operators in the northern areas of China. METHODS: A quota sampling method was used to study 1921 agricultural machinery operators in 5 provinces in northern China. Agricultural machinery injuries that occurred between July 1, 2008, and June 30, 2009 were investigated. Data on nonfatal injuries and related factors were obtained by in-person interviews. RESULTS: The prevalence of agricultural machinery-related injuries among the surveyed operators was 13.1%. Being male, having lower family income and/or poor hearing, being in debt, and feeling stressed were five significant risk factors for injuries. The majority of injuries took place on farmlands (46.6%), roads (26.3%), or in backyards (17.5%). The four most common causes of injuries were being stuck by starting handles that slipped, being slashed or stabbed by sharp objects, being struck by falling objects, and falls from stationary vehicles. CONCLUSIONS: The prevalence of agricultural machinery-related injuries in our study was high. Males, low family income, poor hearing, and stress were associated with high risk of injury occurrence.

Association between the TPH1 A218C polymorphism and risk of mood disorders and alcohol dependence: evidence from the current studies.

BACKGROUND: Several studies have assessed the association between genetic polymorphisms of tryptophan hydroxylase (TPH1) and risk of mood disorders and alcohol dependence, with controversial results. Our aim was to assess the association of TPH1 A218C polymorphism (rs1800532) with mood disorders, including major depressive disorder and bipolar disorder, and alcohol dependence by using meta-analysis. METHODS: Data were collected from the related literatures published until November 25, 2010 from MEDLINE, EMBASE and ISI Web of Science databases, and meta-analysis stratified by ethnicity was performed in either fixed or random effect model as appropriate by using Stata Statistical Package (version 10.0). RESULTS: Twenty-seven individual studies were included in the current study, among which, there were 9 studies for bipolar disorder, with 1951 cases and 2161 controls, 14 studies for major depressive disorder, with 2340 cases and 3204 controls, and 4 studies for alcohol dependence, with 601 cases and 711 controls. We found that in Caucasian population, the TPH1 218AA genotype was significantly associated with increased bipolar disorder risk (recessive comparison: OR, 1.42; Bonferroni-adjusted P=0.006; homozygote comparison: OR, 1.63; Bonferroni-adjusted P=0.072), and elevated alcohol dependence risk (recessive comparison: OR, 1.83; Bonferroni-adjusted P=0.012), while the association was not significant in Asian population. Moreover, the A218C polymorphism did not appear to have any effect on major depressive disorder risk either in Caucasians or in Asians. CONCLUSION: The TPH1 A218C polymorphism is a potential biomarker for bipolar disorder and alcohol dependence risk in Caucasian population.

Ethnic-specific meta-analyses of association between the OPRM1 A118G polymorphism and alcohol dependence among Asians and Caucasians.

BACKGROUND: Many studies have investigated the association between the OPRM1 A118G polymorphism (rs1799971) and alcohol dependence, but the results were inconsistent. To better understand this relationship, ethnicity-specific meta-analyses were conducted. METHODS: We retrieved all eligible studies published up to April 12, 2011 from the PubMed/MEDLINE, EMBASE, and ISI Web of Science databases. Ethnicity-specific meta-analyses were performed using either fixed- or random-effect models as appropriate. RESULTS: Twelve independent studies with 1900 cases and 2382 controls were included. Five studies were conducted in Asians and seven in Caucasians. Ethnicity-specific meta-analyses revealed that the A118G polymorphism was significantly associated with alcohol dependence risk in Asians (GA vs. AA: odds ratio [OR], 1.73; 95% confidence interval [CI], 1.33-2.25; GA+GG vs. AA: OR, 1.57; 95% CI, 1.22-2.02), but not in Caucasians (GA vs. AA: OR, 1.05; 95% CI, 0.75-1.49; GA+GG vs. AA: OR, 1.11; 95% CI, 0.79-1.55). CONCLUSIONS: The OPRM1 A118G polymorphism may contribute to the susceptibility of alcohol dependence in Asians but not in Caucasians.