Evaluating chromosomal damage in workers exposed to hexavalent chromium and the modulating role of polymorphisms of DNA repair genes

Purpose

Welders have been chronically exposed to hexavalent chromium with potential consequences on chromosomal integrity. Our study is focused on the extent of any such chromosomal aberrations with respect to chromium levels in the blood of welders as well as on the tentative modulating role of polymorphisms in DNA repair genes XPD Lys751Gln, XPG Asn114His, XPC Lys939Gln, hOGG1 Ser326Cys and XRCC1 Arg399Gln on chromosomal damage.

Methods

The study was conducted on 144 individuals consisting of 73 welders exposed to chromium for 10.2?±?1.67?years and 71 control individuals without known exposures. Chromosomal aberrations, their chromatid-type and chromosome-type aberrations were detected by conventional cytogenetic analysis. XPD, XPG, XPC, hOGG1 and XRCC1 gene polymorphisms were assayed for by Taqman SNP genotyping assay (“Assay-by-Demand”) using Real-Time allelic discrimination on AB 7500 equipment. Chromium concentration in the blood was determined by atomic absorption spectrophotometry.

Results

The level of chromium in the blood of welders ranged between 0.032 and 0.182?μmol?l^?1 and was significantly higher than that in controls (0.07?±?0.04?μmol?l^?1 vs. 0.03?±?0.007?μmol?l^?1). Parameters of chromosomal damage were similar in both the exposed and the control individuals (1.89% vs. 1.70% for total chromosomal aberrations, 0.97% vs. 0.88% for chromosome-type and 0.92% vs. 0.80% for chromatid-type, respectively). Chromatid-type of aberrations positively correlated with the level of chromium in the blood (r?=?0.28; P?=?0.02). Significantly higher total chromosomal aberrations were detected in individuals with homozygous variant polymorphism in XRCC1 Arg399Gln gene as compared to those with heterozygous and homozygous wild-type genotypes (2.20, 1.89 and 1.48%, respectively; P?=?0.01). A similar tendency was found for chromatid-type aberrations (1.30% for homozygous variant genotype bearers, 0.94% for those with heterozygous genotype and 0.75% for carriers of homozygous wild-type genotype, respectively; P?=?0.04).

Conclusions

Although no apparent increase in chromosomal damage was recorded in chromium-exposed welders in comparison with controls, genetic make-up in DNA repair genes may increase susceptibility toward adverse effect of chromium.     

Lung function in asbestos-exposed workers, a systematic review and meta-analysis

Background

A continuing controversy exists about whether, asbestos exposure is associated with significant lung function impairments when major radiological abnormalities are lacking. We conducted a systematic review and meta-analysis in order to assess whether asbestos exposure is related to impairment of lung function parameters independently of the radiological findings.

Methods

MEDLINE was searched from its inception up to April 2010. We included studies that assessed lung function parameters in asbestos exposed workers and stratified subjects according to radiological findings. Estimates of VC, FEV₁ and FEV1/VC with their dispersion measures were extracted and pooled.

Results

Our meta-analysis with data from 9,921 workers exposed to asbestos demonstrates a statistically significant reduction in VC, FEV₁ and FEV₁/VC, even in those workers without radiological changes. Less severe lung function impairments are detected if the diagnoses are based on (high resolution) computed tomography rather than the less sensitive X-ray images. The degree of lung function impairment was partly related to the proportion of smokers included in the studies.

Conclusions

Asbestos exposure is related to restrictive and obstructive lung function impairment. Even in the absence of radiological evidence of parenchymal or pleural diseases there is a trend for functional impairment.     

Assessment of DNA damage using chromosomal aberrations assay in lymphocytes of waterpipe smokers

Objectives

The aim of this study was to investigate the genotoxicity of waterpipe smoking in the lymphocytes of waterpipe smokers using chromosomal aberrations (CAs) assay.

Materials and Methods

Fifty waterpipe smokers and 18 healthy non-smokers volunteered to participate in the study. Additionally, 18 heavy cigarette smokers were recruited for comparison. Chromosomal aberrations (CAs) assay was used to evaluate DNA damage in the lymphocytes.

Results

The results showed that similarly to cigarette smoking, waterpipe smoking significantly increased the frequencies of CAs (p < 0.01). In addition, the frequencies of CAs increased with more waterpipe use.

Conclusions

Waterpipe smoking causes DNA damage to lymphocytes and the damage increases with more waterpipe use.     

<Emphasis Type="Italic">SEPP1</Emphasis> polymorphisms modulate serum glucose and lipid response to Brazil nut supplementation

Purpose

The consumption of Brazil nuts has been associated with benefits to lipid metabolism and reductions in total cholesterol and LDL concentrations. They are the richest natural source of selenium which has essential functions in human physiology. Genetic polymorphisms in Selenoprotein P could impair lipid and glucose metabolisms. The aim of this work was to verify the influence of polymorphisms in genes for selenoproteins on blood lipid levels after dietary supplementation with Brazil nuts in healthy adults.

Methods

The study included 130 healthy volunteers selected at the University of São Paulo, Brazil. They were supplemented with one nut a day for 8 weeks, followed by 8 weeks without intervention. The following analyses were performed: anthropometric measurements, serum fasting glucose, lipid profile, C-reactive protein and plasma MDA levels. The volunteers were genotyped for SNPs rs1050450, rs3811699, rs1800699, rs713041, rs3877899, rs7579, rs34713741, and rs5845 in genes for selenoproteins.

Results

The concentrations of total cholesterol and fasting glucose levels decreased after 8 weeks of supplementation (p < 0.05). Glucose levels were modulated by rs3877899 in SEPP1, with significantly lower levels observed for individuals with the GA + AA genotype (p = 0.025). In addition, rs7579 was associated with cholesterol concentrations, which were significantly lower for individuals with the GG genotype (p = 0.053).

Conclusions

Supplementation with one Brazil nut a day for 8 weeks reduced total cholesterol and glucose levels. Furthermore, our results suggest that rs3877899 might be associated with glucose concentrations and rs7579 with cholesterol concentrations. Therefore, the effect of genetic variations should be considered in future nutritional interventions evaluating the response to Brazil nut supplementation.

     

Decreased PM10 Exposure Attenuates Age-Related Lung Function Decline: Genetic Variants in p53, p21, and CCND1 Modify This Effect

Background

Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution.

Objective

We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF_25–75) associated with improved air quality.

Methods

Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter ≤ 10 μm (PM₁₀) to each participant’s residential history 12 months before the baseline and follow-up assessments.

Results

The effect of diminishing PM₁₀ exposure on FEF_25–75 decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-μg/m³ decline in aver-age PM₁₀ exposure over an 11-year period attenuated the average annual decline in FEF_25–75 by 21.33 mL/year (95% confidence interval, 10.57–32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38–22.06) among GA genotypes, and by 6.00 mL/year (−4.54 to 16.54) among AA genotypes.

Conclusions

Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults.     

A cytogenetic approach to the effects of low levels of ionizing radiation (IR) on the exposed Tunisian hospital workers

Objectives

The aim of this study is to assess chromosomal damage in Tunisian hospital workers occupationally exposed to low levels of ionizing radiation (IR).

Materials and Methods

The cytokinesis-block micronucleus (CBMN) assay in the peripheral lymphocytes of 67 exposed workers compared to 43 controls matched for gender, age and smoking habits was used. The clastogenic/aneugenic effect of IR was evaluated using the CBMN assay in combination with fluorescence in situ hybridization with human pan-centromeric DNA in all the exposed subjects and controls.

Results

The study showed a significant increase of the micronucleus (MN) frequency in the lymphocytes of the exposed workers compared to the control group (13.63±4.9‰ vs. 6.52±4.21‰, p < 0.05). The centromere analysis performed in our study showed that MNs in hospital staff were predominantly centromere negative (72%) and the mean negative labeled micronucleus (C-MN) frequency was significantly higher in the exposed subjects than in the controls (9.04±4.57‰ vs. 1.17±0.77‰). The multivariate regression analysis, taking into account all confounding factors, showed that only the time of exposure to IR had a significant effect on the level of MNs and C-MN.

Conclusion

The present study shows that chromosomal damage leading to the formation of micronucleated lymphocytes is more frequent in the hospital workers exposed to IR than in the controls, despite the low levels of exposure. The results of the study confirm the well-known clastogenic properties of ionizing radiation. In regards to health monitoring, detection of early genotoxic effects may allow for the adoption of preventive biological control measures, such as hygienic improvements in the workplace or reduction of hours of occupational exposure.     

Biomarkers of exposure in Monday morning urine samples as a long-term measure of exposure to aromatic diisocyanates

Purpose

Exposure to diisocyanates is a known occupational hazard. One method for monitoring occupational exposure is by analyzing biomarkers in hydrolyzed urine and plasma. The half-life of the biomarkers in plasma is about 3 weeks, and the urinary elimination is divided into one fast (hours) and one slow phases (weeks). Polymorphism in glutathione S-transferase enzymes (GST) is earlier shown to modify the metabolism. The aim of the study was to assess whether biomarkers of exposure in urine collected after two non-exposed days correlate with levels in plasma and whether they can be used as a measure for long-term exposure to aromatic diisocyanates and further whether polymorphisms in GST influenced the correlations.

Methods

Biomarkers of exposure was analyzed in urine and blood samples collected from 24 workers, exposed to at least one of toluene-, methylenediphenyl- or naphthalene diisocyanate, on a Monday morning after at least two unexposed days. Moreover, genotype was determined for 19 of the workers.

Results

The corresponding specific gravity-adjusted biomarkers in urine and plasma levels for the different diisocyanates correlated well (r between 0.689 and 0.988). When taking all samples together, the correlation coefficient was 0.926. Polymorphism in the GSTM1 genotype seemed to modify the association.

Conclusion

Urine collected after two unexposed days can possibly be used as long-term biomarker of exposure for aromatic diisocyanates.     

Associations of buccal cell telomere length with daily intake of β-carotene or α-tocopherol are dependent on carotenoid metabolism-related gene polymorphisms in healthy Japanese adults

Objective

Telomere length shortening is modulated not only by aging, but also by both genetic and environmental factors. The aim of this study was to investigate the interactions between antioxidant nutrient metabolism-related gene single nucleotide polymorphisms (the genetic factors) and nutrient intake (the environmental factors) in their effects on telomere length shortening.

Setting & participants

Data were collected on the relative telomere lengths (RTLs) of buccal cells and the habitual food intake of 70 healthy Japanese adults.

Measurements

All subjects were genotyped for two common single nucleotide polymorphisms: rs6564851 in the β-carotene-15,15’-mono-oxygenase 1 (BCMO1) gene and rs362090 in the intestine-specific homeobox (ISX) gene.

Results

Univariate analysis revealed that buccal RTL was not significantly modulated by either age or gender. Then, we subdivided the study population into four groups based on combinations of the rs6564851 and rs362090 genotypes. After this subdivision, we showed a positive effect of daily α- or β-carotene intake on buccal RTL in the ISX rs362090 G-allele carrier + BCMO1 rs6564851 GG-genotype group (p = 0.026). Additionally, daily intake of another antioxidative fat-soluble vitamin, α-tocopherol, was positively associated with buccal RTL in the ISX rs362090 AA-homozygote + BCMO1 rs6564851 T-allele carrier group (p = 0.037).

Conclusion

Our study clearly indicates that high dietary intake of the antioxidants α, β-carotene and α-tocopherol protects buccal cells from RTL shortening, depending on the genetic background of antioxidant vitamin-related genes.

     

Correlation of chromosome damage and promoter methylation status of the DNA repair genes MGMT and hMLH1 in Chinese vinyl chloride monomer (VCM)-exposed workers

Objective

To explore the association of the methylation status of MGMT and hMLH1 with chromosome damage induced by vinyl chloride monomer (VCM).

Materials and Methods

Methylation of MGMT and hMLH1 was measured in 101 VCM-exposed workers by methylation-specific PCR. Chromosome damage in peripheral blood lymphocytes was measured by the cytokinesis-block micronucleus assay. The subjects were divided into chromosome damaged and non-damaged groups based on the normal reference value of micronuclei frequencies determined for two control groups.

Results

MGMT promoter methylation was detectable in 5 out of 49 chromosome damaged subjects, but not in the chromosome non-damaged subjects; there was a significant difference in MGMT methylation between the two groups (p < 0.05).

Conclusions

We detected aberrant promoter methylation of MGMT in a small number of chromosome damaged VCM-exposed workers, but not in the chromosome non-damaged subjects. This preliminary observation warrants further investigation in a larger study.     

Diallyl trisulfide-induced prostate cancer cell death is associated with Akt/PKB dephosphorylation mediated by P-p66shc

Purpose

P66Shc, an isoform of adaptor proteins, is known to mediate various signals including those leading to apoptosis or cell proliferation. Previously, we have shown that diallyl trisulfide (DATS)-induced prostate cancer cell death was mediated by increased ROS formation. In this study, we investigated the role of p66Shc protein and its serine 36 phosphorylation in DATS induced decrease in prostate cancer cell viability (PC-3).

Methods

PC-3 prostate cancer cells were used in this study. Stable cell lines expressing p66ShcS36A or an empty vector have been obtained. Cell viability, concentration of ROS, changes in P-p66Shc and P-Akt and DNA damage were determined.

Results

We observed that DATS treatment increased p66Shc phosphorylation at serine 36. Importantly, the phosphorylation was abolished by JNK inhibitor SP600125. Cells expressing plasmid-encoded variant of p66ShcS36A showed much higher resistance to DATS-induced cells death. In addition to that, we observed that DATS-induced ROS formation was completely abolished in cells expressing the p66ShcS36A variant. Interestingly, SP600125 proved to prevent DATS-induced Akt inactivation. In order to confirm that the observed effect is related to phosphorylation of p66Shc, we performed experiments on a stable cell line expressing p66ShcS36A. In such cells, DATS-induced Akt dephosphorylation was significantly reduced. On the other hand, hydrogen peroxide induced Akt activation in PC-3 cells, which was abrogated in cells expressing p66ShcS36A.

Conclusions

Our results uncover a novel signaling pathway with p66Shc being indispensable for DATS-induced inactivation of Akt due to hypophosphorylation.     

Moderate effects of apple juice consumption on obesity-related markers in obese men: impact of diet–gene interaction on body fat content

Purpose

The effect of polyphenol-rich cloudy apple juice (CloA) consumption on plasma parameters related to the obesity phenotype and potential effects of interactions between CloA and allelic variants in obesity candidate genes were assessed in obese men.

Methods

In this controlled, randomized, and parallel study, n?=?68, non-smoking, non-diabetic men with a BMI ≥27?kg/m² received 750?mL/day CloA (802.5?mg polyphenols) or 750?mL/day control beverage (CB, isocaloric equivalent to CloA) for 4?weeks. Further, study participants were genotyped for single-nucleotide polymorphisms in PPARγ (rs1801282), UCP3 (rs1800849), IL-6 (rs1800795), FABP2 (rs1799883), INSIG2 (rs7566605), and PGC1 (rs8192678) genes. At the beginning and at the end of intervention plasma lipids, distinct adipokines and cytokines as well as anthropometric parameters were determined.

Results

CloA compared to CB had no significant effect on plasma lipids, plasma adipokine and cytokine levels, BMI, and waist circumference. However, CloA consumption significantly reduced percent body fat compared to CB (? % body fat: CloA: ?1.0?±?1.3 vs. CB: ?0.2?±?0.9, p?Conclusion The observed diet–gene interaction might be a first indication for the impact of individual genetic background on CloA-mediated bioactivity on obesity-associated comorbidities.     

Observations of Group Care Worker-Child Interaction in Residential Youth Care: Pedagogical Interventions and Child Behavior

Background

The work of group care workers in residential youth care is often described as professional parenting. Pedagogical interventions of group care workers influence the quality of care for looked-after children.

Objective

The aim of the current study was to observe the pedagogical interventions of group care workers within residential youth care and their associations with child behaviors.

Methods

Group care worker interventions and child behaviors were videotaped during structured observations. Participants included 95 children (64 % boys, M _age = 9.19) and 53 group care workers (74 % female, M _age = 33.79 years). A coding system was developed to code pedagogical interventions and child behaviors.

Results

It showed that group care workers mainly used positive pedagogical interventions (warmth/support and positive control) and seldom used negative pedagogical interventions (permissiveness and negative control). Frustration and anger of children was associated with positive controlling interventions and permissiveness of group care workers. The hypothesis that child anxiety and nervousness is associated with warm and supportive interventions could not be confirmed.

Conclusions

Pedagogical interventions should be part of education, training, and supervision of group care workers.     

Is there a role for carbohydrate restriction in the treatment and prevention of cancer?

Background

Aflatoxin B1 (AFB1) is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE) on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA) level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver.

Methods

Adult, healthy balbC (20-25 g) male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks.

Results

Our results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i) a total reduction of AFB1 induced oxidative damage markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii) restriction of the effect of AFB1 by differential modulation of the expression of p53 which decreased as well as its associated genes such as bax and bcl2.

Conclusion

We concluded that CCE might have a hepatoprotective effect against aflatoxicosis in mice, probably acting by promoting the antioxidant defence systems.     

Selected Polymorphisms of Base Excision Repair Genes and Pancreatic Cancer Risk in Japanese

Background

Although several reports have described a possible association between DNA repair genes and pancreatic cancer (PC) in smokers, this association has not been fully evaluated in an Asian population. We assessed the impact of genetic polymorphisms in the base excision repair (BER) pathway on PC risk among Japanese.

Methods

This case-control study compared the frequency of 5 single-nucleotide polymorphisms (SNPs) of BER genes, namely rs1052133 in OGG1, rs1799782 and rs25487 in XRCC1, rs1130409 in APE1, and rs1136410 in PARP1. SNPs were investigated using the TaqMan assay in 185 PC cases and 1465 controls. Associations of PC risk with genetic polymorphisms and gene–environment interaction were examined with an unconditional logistic regression model. Exposure to risk factors was assessed from the results of a self-administered questionnaire. We also performed haplotype-based analysis.

Results

We observed that the minor allele of rs25487 in XRCC1 was significantly associated with PC risk in the per-allele model (odds ratio = 1.29, CI = 1.01–1.65; trend P = 0.043). Haplotype analysis of XRCC1 also showed a statistically significant association with PC risk. No statistically significant interaction between XRCC1 polymorphisms and smoking status was seen.

Conclusions

Our findings suggest that XRCC1 polymorphisms affect PC risk in Japanese.Key words: pancreatic cancer, SNPs, DNA repair gene, XRCC1     

Comparison of the level of aggression towards healthcare workers within Podlaskie Voivodeship

Objectives

The aim of this study was to estimate the level of exposure and average intensity of aggression towards particular professional groups of healthcare workers.

Materials and Methods

Study participants (n = 1498) were employed at open and closed healthcare units within Podlaskie Voivodeship: 493 nurses, 504 midwives and 501 physicians. The MDM Questionnaire was applied.

Results

Aggression originating from patients was experienced by 92% of nurses, 86% of doctors, and 74% of midwives examined. Aggressive behavior of co-working physicians concerned 55% of midwives, 54% of nurses and 40% of physicians. The highest average levels of patient aggression, ranging between 2.20 and 3.31, were reported by nurses.

Conclusions

Nurses are the group most exposed to most aggression forms and sources. Physicians are least exposed to aggression, except for aggression manifested by patients.     

Failure to detect significant association between estrogen receptor-alpha gene polymorphisms and endometriosis in Japanese women

Objectives

The aim of the study was to test whether estrogen receptor 1 (ESR1) gene polymorphisms are correlated with the risk of the development of endometriosis in Japanese women, as a preliminary study.

Methods

To compare allelic frequencies and genotype distributions, a case-control study of 100 affected women and 143 women with no evidence of disease was performed using 10 microsatellite repeat markers and 66 single-nucleotide polymorphisms (SNPs) in the ESR1 gene region.

Results

Although our results might be insufficient to detect genetic susceptibility, owing to the small sample size and low genetic power, statistical analysis of the differences in allelic frequency between the cases and controls at each microsatellite locus demonstrated that no microsatellite locus in the ESR1 gene displayed a significant association with the disease when multiple testing was taken into account. Also, there were no statistically significant differences in the SNP allele frequencies and genotypes between the cases and controls when multiple testing was taken into account.

Conclusion

The findings in our pilot study suggest that ESR1 polymorphisms do not contribute to endometriosis susceptibility.     

The genotype of the transporter associated with antigen processing gene affects susceptibility to colorectal cancer in Japanese

Objective

Although colorectal cancer (CRC) is one of the most frequent malignancies in Japan, the associated genetic factors remain to be elucidated. Functional loss of the transporter associated with antigen processing (TAP) 1 gene induces carcinogenesis. We investigated whether single nucleotide polymorphisms (SNPs) in the TAP1 gene (rs735883) are associated with susceptibility to CRC in a Japanese population.

Methods

The study participants were 143 cases and 243 clinical controls. After extracting DNA from their peripheral blood cells, genotyping was conducted by the polymerase chain reaction–restriction fragment length polymorphism method.

Results

Participants with a mutated allele had an increased risk for CRC. The adjusted odds ratios for the C/T, T/T, and the mutation type (C/T + T/T) compared to that of wild type (C/C) were 2.27 [95 % confidence interval (CI), 1.43–3.67], 1.95 (95 % CI, 0.88–4.30), and 2.22 (95 % CI, 1.42–3.55), respectively. Furthermore, a significant trend in the rate of cases was observed with an increasing number of mutated alleles (P for trend = 0.0068).

Conclusions

The genotype of the TAP1 gene is associated with susceptibility to CRC.     

The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis

Background

Glutathione has a wide range of functions; it is an endogenous anti-oxidant and plays a key role in the maintenance of intracellular redox balance and detoxification of xenobiotics. Several studies have indicated that children with autism spectrum disorders may have altered glutathione metabolism which could play a key role in the condition.

Methods

A systematic literature review and meta-analysis was conducted of studies examining metabolites, interventions and/or genes of the glutathione metabolism pathways i.e. the ??-glutamyl cycle and trans-sulphuration pathway in autism spectrum disorders.

Results

Thirty nine studies were included in the review comprising an in vitro study, thirty two metabolite and/or co-factor studies, six intervention studies and six studies with genetic data as well as eight studies examining enzyme activity.

Conclusions

The review found evidence for the involvement of the ??-glutamyl cycle and trans-sulphuration pathway in autistic disorder is sufficiently consistent, particularly with respect to the glutathione redox ratio, to warrant further investigation to determine the significance in relation to clinical outcomes. Large, well designed intervention studies that link metabolites, cofactors and genes of the ??-glutamyl cycle and trans-sulphuration pathway with objective behavioural outcomes in children with autism spectrum disorders are required. Future risk factor analysis should include consideration of multiple nutritional status and metabolite biomarkers of pathways linked with the ??-glutamyl cycle and the interaction of genotype in relation to these factors.     

<Emphasis Type="Italic">ANGPTL4</Emphasis> variants and their haplotypes are associated with serum lipid levels,the risk of coronary artery disease and ischemic stroke and atorvastatin cholesterol-lowering responses

Background

This study aimed to assess the association between the angiopoietin-like protein 4 gene (ANGPTL4) single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS), and response to atorvastatin therapy in a Southern Chinese Han population.

Methods

Genotypes of the ANGPTL4 rs4076317, rs7255436, rs1044250 and rs2967605 SNPs in 1,654 unrelated subjects (CAD, 568; IS, 537; and controls, 549) were determined by the Snapshot technology. Another group of 724 hyperlipidemic patients was selected and treated with atorvastatin calcium tablet 20 mg/day for 8 weeks.

Results

The rs2967605 CT/TT genotypes were associated with a decreased risk of CAD (adjusted OR = 0.68, 95% CI = 0.47-0.99, P = 0.043 for CT/TT vs. CC) and IS (adjusted OR = 0.55, 95% CI = 0.38-0.80, P = 0.020 for CT/TT vs. CC). There was no significant association between the four SNPs and angiographic severity of CAD. The subjects with the rs4076317 CG/CC genotypes in controls had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than the subjects with the GG genotype (P < 0.001; a P < 0.0018 was regarded statistically significant by the Bonferroni correction). The subjects with rs4076317CG/GG genotypes had lower TC and LDL-C levels than the subjects with CC genotype after atorvastatin treatment (P < 0.001).

Conclusions

The observed associations suggest that the ANGPTL4 variants have a potential role on serum lipid levels and atherosclerosis-related diseases in the Chinese Han population, especially the ANGPTL4 rs4076317 and rs2967605 SNPs.

     

Gene- gene interaction between PPARG and APOE gene on late-onset Alzheimer’s disease: A case- control study in Chinese han population

Aims

The aim was to investigate the impact of PPARG and APOE gene single nucleotide polymorphisms (SNPs) and additional gene- gene interaction on late-onset Alzheimer’s disease (LOAD) risk based on Chinese Han population.

Methods

A total of 928 participants (466 males, 462 females), with a mean age of 81.3 ± 16.4 years old, were included in the study, including 460 LOAD patients and 468 normal controls participants. Logistic regression was performed to investigate association between SNP and LOAD risk and generalized multifactor dimensionality reduction (GMDR) was used to analysis the gene-gene interaction.

Results

Logistic regression analysis showed that LOAD risk was significantly higher in carriers of G allele of the rs405509 polymorphism than those with AA (AG+ GG versus AA, adjusted OR (95%CI) =1.54(1.20-1.89), and higher in carriers of G allele of the rs1805192 polymorphism than those with CC (CG+ GG versus CC, adjusted OR (95%CI) =1.32(1.16-2.43). We also found that there was a potential gene–gene interaction between rs405509 and rs1805192. Participants with AG or GG of rs405509 and CG or GG of rs1805192 genotype have the highest AD risk, compared to participants with AA of rs405509 and CC of rs1805192 genotype, OR (95%CI) was 2.62(1.64 -3.58), after covariates adjustment.

Conclusions

G allele of the rs405509 of APOE and G allele of the rs1805192 of PPAR G polymorphism were associated with increased LOAD risk, and participants with AG or GG of rs405509 and CG or GG of rs1805192 genotype have the highest AD risk.