Genetic Polymorphisms of Endothelial Nitric Oxide Synthase Associated with Hypertension and Blood Homocysteine Levels

Charinya Chaichanabut,1 Piyamitr Sritara,2 Jintana Sirivarasai3 1Master of Science Program in Nutrition, Faculty of Medicine Ramathibodi Hospital and Institute of Nutrition, Mahidol University, Bangkok, Thailand; 2Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Nutrition Unit, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Jintana Sirivarasai, Nutrition Unit, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand, Tel +662-201-1483, Fax +662-201-2625, Email [email protected]: Endothelial dysfunction is a key mechanism in the development of hypertension and is closely linked to impairment of endothelial nitric oxide synthase (eNOS) and hyperhomocysteinemia. Genetic polymorphisms of eNOS (rs1799983 and rs2070744) are strongly associated with the risk of hypertension in individuals of Asian ethnicities. This study aimed to investigate the relationship between these polymorphisms and the risk of hypertension associated with homocysteine levels.Participants and Methods: For this cross-sectional study, we enrolled 370 Thai men aged 40– 60 years from the Electricity Generating Authority of Thailand cohort study for both variants genotyping by TaqMan allelic discrimination analysis. Clinical, anthropometric, and biochemical parameters were also analyzed.Results: In the high blood pressure group (n = 267), systolic and diastolic blood pressure and triglyceride levels were higher in those with homocysteine levels ≥ 15 μmol/L than in those with homocysteine levels < 15 μmol/L (p < 0.05). Significant risk of hypertension was found in GG and GT of rs1799983 (G894T), and in TT and TC of rs2070744 (T-786C), with higher ORs in heterozygous genotypes (all p values < 0.05). Further evaluation of the interactions between SNPs and HCY revealed that individuals with the GT or TC genotype, together with hyperhomocysteinemia, had an increased risk of hypertension (all p< 0.05).Conclusion: eNOS variants rs1799983 and rs2070744 may be risk factors for hypertension linked to hyperhomocysteinemia. These findings provide potentially useful healthcare strategies for the management of hypertension.Keywords: endothelial nitric oxide synthase, polymorphisms, hypertension, hyperhomocysteinemi

Blood lead, cadmium and mercury among children from urban, industrial and rural areas of Fez Boulemane Region (Morocco): Relevant factors and early renal effects

Objectives: To describe blood lead (Pb-B), cadmium (Cd-B) and mercury (Hg-B) levels in children living in urban, industrial and rural areas in Fez city (north of Morocco) and to identify the determinants and some renal effects of exposure. Material and Methods: The study was conducted from June 2007 to January 2008 in 209 school children (113 girls, 96 boys), aged 6-12 years, from urban, industrial and rural areas in Fez city. Interview and questionnaires data were obtained. Blood and urinary samples were analyzed. Results: The mean of blood lead levels (Pb-B) in our population was 55.53 μg/l (range: 7.5-231.1 μg/l). Children from the urban area had higher blood lead levels (BLLs) mean (82.36 μg/l) than children from industrial and rural areas (48.23 and 35.99 μg/l, respectively); with no significant difference between boys and girls. BLLs were associated with traffic intensity, passive smoking and infancy in the urban area. The mean of blood cadmium levels (BCLs) was 0.22 μg/l (range: 0.06-0.68 μg/l), with no difference between various areas. Rural boys had higher BCLs mean than rural girls, but no gender influence was noticed in the other areas. BCLs were associated with the number of cigarettes smoked at children's homes. The blood mercury levels (BMLs) mean was 0.49 μg/l (range: 0.01-5.31 μg/l). The BMLs mean was higher in urban and industrial areas than in the rural area with no gender-related difference. BMLs were associated with amalgam fillings and infancy in the urban area. About 8% of the children had BLLs ≥ 100 μg/l particularly in the urban area, microalbuminuria and a decrease in height were noticed in girls from the inner city of Fez and that can be related to high BLLs (89.45 μg/l). Conclusions: There is a need to control and regulate potential sources of contamination by these trace elements in children; particularly for lead

Effects of AGT and AGTR1 Genetic Polymorphisms and Changes in Blood Pressure Over a Five-Year Follow-Up

Siwaphorn Chaimati,1 Prapimporn Chattranukulchai Shantavasinkul,2 Piyamitr Sritara,2 Jintana Sirivarasai3 1Doctoral Program in Nutrition, Faculty of Medicine Ramathibodi Hospital and Institute of Nutrition, Mahidol University, Bangkok, 10400, Thailand; 2Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand; 3Nutrition Division, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, ThailandCorrespondence: Jintana Sirivarasai, Nutrition Division, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand, Tel +662-201-1483, Fax +662-201-2625, Email [email protected]: The renin–angiotensin system plays an important role in the central regulation of blood pressure (BP). Genetic variations of angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1) may increase susceptibility to elevated BP and hypertension. This study investigated the effects of AGT rs699 and AGTR1 rs5186 single nucleotide polymorphisms (SNPs) on BP at baseline and at a 5-year follow-up.Paticipants and Methods: The study population consisted of participants from the Electricity Generating Authority of Thailand cohort study (n=354); data were collected at baseline (2013) and 5 years later (2018). Genotyping of the two SNPs was performed using TaqMan® assay and statistical analyses were performed with SNPStats software.Results: The frequencies of the two SNPs were within the Hardy–Weinberg equilibrium (p=0.22 for AGT rs699 and p=0.06 for AGTR1 rs5186). For each SNP, mutant genotypes were significantly associated with increased systolic BP and/or diastolic BP in the codominant and recessive models. Risk alleles of AGT rs699 and AGTR1 rs5186 were associated with increased odds of hypertension and hypertension with metabolic syndrome at follow-up.Conclusion: Overall, our results suggest that polymorphisms of genes in the renin–angiotensin system increase susceptibility to the development and progression of hypertension and the development of the metabolic syndrome.Keywords: angiotensinogen, angiotensin II receptor type 1, polymorphisms, hypertension, metabolic syndrom

Comparison of urinary biomarkers concentrations in exposed and non-exposed petrol station workers in the Eastern Economic Corridor (EEC), Thailand

Background. The Thai government has been developing its Eastern Economic Corridor (EEC), which spans three provinces, with the aim of improving connections with other Asian nations. Since this strategic development, the number of trucks, private car, and passenger car registrations have continued to grow, with a corresponding increase in related to benzene, toluene, ethylbenzene, and xylene (BTEX). Objectives. This study aims to compare the levels of trans, trans-muconic acid (t, t MA); toluene (TU); mandelic acid (MA); and methyl hippuric acid (MHA) in the urine of gas station employees, considering demographic and occupational factors. Material and methods. These employees worked either near or away from the fuel dispenser, and there 100 people in each group. Data were collected using interviews and testing environmental air and urine samples for benzene, toluene, ethyl benzene, and xylene (BTEX). Results. The results showed that BTEX concentrations were just detectable in all 200 cases (100%). The mean (±SD) urine level of t, t MA was 449.28 (±213.32) μg/g creatinine, while the median (min-max) was 428.23 (95.58-1202.56) μg/g creatinine. The mean TU was 0.011 (0.001) mg/L, while the median (min-max) was 0.011 (0.010-0.013) mg/L. MA levels were higher inside the pollution control zone than they were outside the zone (p=.009). Employees who practiced poor personal hygiene had relatively high urinary toluene and MHA levels (p=.009) and those who did not wear personal protective equipment (PPE) had relatively high MA levels (p=.040). Conclusion. The results of this study revealed statistically significant biomarkers influencing the levels of t, t MA; TU; MA; and MHA in urine. The recommendations of this study are that employers should provide their employees with suitable PPE, check regularly to ensure that it is worn, and strongly encourage employees to take care of their sanitation. Employees should take appropriate breaks and days off to minimize their exposure to BTEX

Association between Dietary Zinc Intake, Serum Zinc Level and Multiple Comorbidities in Older Adults

Zinc is one of the essential micronutrients in the geriatric population, but the importance of zinc status and dietary zinc intake has been poorly characterized. We aimed to explore the relationships among dietary zinc intake, serum zinc concentrations and multimorbidity in a cross-sectional study of 300 employees of Electric Generating Authority of Thailand aged ≥ 60 years. Comprehensive questionnaires were completed, and clinical and laboratory assessments were performed. Factors associated with low serum zinc concentrations were identified using multivariate multinomial logistic regression analyses. The mean serum zinc level was 80.5 (12.8) µg/dL. After adjustment for baseline characteristics, being female and having been in education for ≤12 years were independent risk factors for the lowest tertile (T1) of serum zinc. After additional adjustment for clinical and biochemical parameters, there was a significant association between depression (Thai Geriatric Depression Scale-15 score > 5) and low serum zinc levels (T1 vs. T3, odds ratio (OR): 2.24; 95% confidence interval (CI): 1.06–4.77). Furthermore, as serum albumin increased, serum zinc concentration substantially increased (T1 vs. T3, OR: 0.01; 95% CI: 0.002–0.070). Therefore, the early detection of risk factors and the further management of depression and low serum albumin may assist physicians in preventing low serum concentrations

Role of Dietary Factors on DNA Methylation Levels of TNF-Alpha Gene and Proteome Profiles in Obese Men

Integrated omics-based platforms from epigenomics and proteomics technologies are used to identify several important mechanisms in obesity etiology, food components, dietary intake, regulation of biological pathways, and potential new intervention targets. Therefore, this study aimed to analyze whether dietary factors involved in the methylation of tumor necrosis factor (TNF)-α are implicated in differential protein expression in people with normal weight and obesity. Methods: The participants were classified into the non-obese (N = 100) and obese (N = 133) groups. DNA methylation levels of the TNF-alpha gene and proteomics were analyzed using the pyrosequencing method and LC-MS-MS, respectively. Results: Comparison between geometric means of DNA methylation of TNF-α showed lower levels in subjects with obesity than in those without obesity (p < 0.05). There were associations between dietary factors and some metabolic syndrome components and TNF-α DNA methylation levels. Proteomic analysis showed important signaling pathways related to obesity, with 95 significantly downregulated proteins and 181 upregulated proteins in the non-obese group compared with the obese group. Conclusion: This study shows an association between the dietary factors involved in the methylation of TNF-α and differential protein expression related to obesity. However, a large sample size in future studies is required to confirm our results

Novel Serum Proteomes Expressed from Benzene Exposure Among Gasoline Station Attendants

Background: Research on the proteomes impact of benzene exposure in fuel station employees remains sparse, underscoring the need for detailed health impact assessments focusing on biomarker evaluation. Objectives: This investigation aimed to analyze the differences in blood parameters and serum proteomes resulting from benzene exposure between gasoline station attendants (B-GSA) and a control group. Design and methods: A cross-sectional analytical study was conducted with 96 participants, comprising 54 in the B-GSA group and 42 in the control group. The methodology employed included an interview questionnaire alongside urine and blood sample collections. The urine samples were analyzed for trans,trans -muconic acid ( t,t -MA) levels, while the blood samples underwent complete blood count analysis and proteome profiling. Results: Post-shift analysis indicated that the B-GSA group exhibited significantly higher levels of t,t -MA and monocytes compared to the control group ( P  < .05). Proteome quantification identified 1448 proteins differentially expressed between the B-GSA and control groups. Among these, 20 proteins correlated with the levels of t,t -MA in urine. Notably, 4 proteins demonstrated more than a 2-fold down-regulation in the B-GSA group: HBS1-like, non-structural maintenance of chromosomes element 1 homolog, proprotein convertase subtilisin/kexin type 4, and zinc finger protein 658. The KEGG pathway analysis revealed associations with apoptosis, cancer pathways, p53 signaling, and the TNF signaling pathway. Conclusion: The changes in these 4 significant proteins may elucidate the molecular mechanisms underlying benzene toxicity and suggest their potential as biomarkers for benzene poisoning in future assessments

Serum Glycoproteomics and Identification of Potential Mechanisms Underlying Alzheimer’s Disease

Objectives. This study compares glycoproteomes in Thai Alzheimer’s disease (AD) patients with those of cognitively normal individuals. Methods. Study participants included outpatients with clinically diagnosed AD (N=136) and healthy controls without cognitive impairment (N=183). Blood samples were collected from all participants for biochemical analysis and for Apolipoprotein E (APOE) genotyping by real-time TaqMan PCR assays. Comparative serum glycoproteomic profiling by liquid chromatography-tandem mass spectrometry was then performed to identify differentially abundant proteins with functional relevance. Results. Statistical differences in age, educational level, and APOE ɛ3/ɛ4 and ɛ4/ɛ4 haplotype frequencies were found between the AD and control groups. The frequency of the APOE ɛ4 allele was significantly higher in the AD group than in the control group. In total, 871 glycoproteins were identified, including 266 and 259 unique proteins in control and AD groups, respectively. There were 49 and 297 upregulated and downregulated glycoproteins, respectively, in AD samples compared with the controls. Unique AD glycoproteins were associated with numerous pathways, including Alzheimer’s disease-presenilin pathway (16.6%), inflammation pathway mediated by chemokine and cytokine signaling (9.2%), Wnt signaling pathway (8.2%), and apoptosis signaling pathway (6.7%). Conclusion. Functions and pathways associated with protein-protein interactions were identified in AD. Significant changes in these proteins can indicate the molecular mechanisms involved in the pathogenesis of AD, and they have the potential to serve as AD biomarkers. Such findings could allow us to better understand AD pathology