Association of Endothelin-Converting Enzyme and Endothelin-1 Gene Polymorphisms with Essential Hypertension in Malay Ethnics.

Objectives: Endothelin-1 (ET-1), the most potent endogenous vasoconstrictor, generated by enzymatic cleavage catalyzed by an endothelin-converting enzyme (ECE), plays a significant role in the regulation of hypertension. Methods: This study investigates the effect of endothelin-1 (Lys198Asn/rs5370) and ECE (rs212526 C/T) gene polymorphisms with essential hypertension (EH) among Malay ethnics. To determine the association of gene polymorphism, 177 hypertensives and controls (196) were genotyped using Taqman method. Results: A significant difference was observed in ET-1 rs5370 and ECE rs212526 gene polymorphisms between EH and control subjects (P < 0.001). A significantly high body mass index (BMI), waist-to-hip ratio, fasting plasma glucose, hemoglobin A1c, systolic and diastolic blood pressure, and lipid profiles were observed among the EH patients when compared to controls (P < 0.05). Moreover, T allele (rs5370) carriers in males have a high risk for EH. There was no significant association between gender in ECE C/T polymorphisms (P > 0.05). Conclusion: Based on our result, it is evident that the T allele of ET-1 rs5370 polymorphism and C allele of ECE rs212526 have a significant genetic risk factor in EH among Malay subjects, and BMI and age are associated with hypertension.

Homologous recombination repair gene mutations in Malaysian prostate cancer patients.

Genetic alterations in the homologous recombination repair (HRR) genes are associated with an increased risk of prostate cancer development, and patients harboring these mutations can benefit from targeted therapy. The main aim of this study is to identify genetic alterations in HRR genes as a potential target for targeted treatment. In this study, targeted next generation sequencing (NGS) is used to analyze mutations in the protein-coding regions of the 27 genes involved in HRR and mutations in hotspots of 5 cancer-associated genes in four FFPE samples and three blood samples from prostate cancer patients. We identified two mutations in TP53 and KRAS. We also identified four conflicting interpretations of pathogenicity variants in BRCA2, STK11 genes and one variant of uncertain significance in the RAD51B gene. In addition, we detected one drug response variant in TP53, and two novel variants in CDK12 and ATM. Our results revealed some actionable pathogenic and potential pathogenic variants that may be associated with response to the Poly (ADP-ribose) polymerase (PARP) inhibitor treatment. More studies in a larger cohort are needed to evaluate and determine the association of HRR mutations with prostate cancer.

Haplotype Analysis of ß-Thalassaemia Major and Carriers with Filipino ß°-Deletion in Sabah, Malaysia.

OBJECTIVE: The Filipino ß°-deletion has been reported as a unique mutation in East Malaysia with a severe phenotype due to the complete absence of ß-globin chain synthesis. In this study, the haplotype patterns of the ß-globin gene cluster were used to relate the human genetic variation to this specific ß-thalassaemia mutation. METHODS: The 376 study subjects included 219 ß-thalassaemia major (ß-TM) patients with homozygous Filipino ß°-deletion and 157 carriers with heterozygous Filipino ß°-deletion from 10 government hospitals in different regions of Sabah. Genomic DNA was isolated from whole blood using silica membrane based DNA purification protocol. Polymerase chain reaction restriction fragment length polymorphism analysis (PCR-RFLP) was conducted on five markers within the ß-globin gene cluster to construct the haplotype patterns. RESULTS: Four haplotypes (Haplotype I-IV) were identified with Haplotype I as the predominant haplotype with the highest frequency of 0.98, followed by Haplotype II, III and Haplotype IV with 0.02. Haplotype I was strongly linked with the Filipino ß°-deletion among the indigenous population. CONCLUSION: Haplotype I as the predominant haplotype suggests the patients with the Filipino ß°-deletion in Sabah have a similar origin.

Red pitaya juice supplementation ameliorates energy balance homeostasis by modulating obesity-related genes in high-carbohydrate, high-fat diet-induced metabolic syndrome rats.

BACKGROUND: Red pitaya (Hylocereus polyrhizus) or known as buah naga merah in Malay belongs to the cactus family, Cactaceae. Red pitaya has been shown to give protection against liver damage and may reduce the stiffness of the heart. Besides, the beneficial effects of red pitaya against obesity have been reported; however, the mechanism of this protection is not clear. Therefore, in the present study, we have investigated the red pitaya-targeted genes in obesity using high-carbohydrate, high-fat diet-induced metabolic syndrome rat model. METHODS: A total of four groups were tested: corn-starch (CS), corn-starch + red pitaya juice (CRP), high-carbohydrate, high-fat (HCHF) and high-carbohydrate, high-fat + red pitaya juice (HRP). The intervention with 5 % red pitaya juice was continued for 8 weeks after 8 weeks initiation of the diet. Retroperitoneal, epididymal and omental fat pads were collected and weighed. Plasma concentration of IL-6 and TNF-α were measured using commercial kits. Gene expression analysis was conducted using RNA extracted from liver samples. A total of eighty-four genes related to obesity were analyzed using PCR array. RESULTS: The rats fed HCHF-diet for 16 weeks increased body weight, developed excess abdominal fat deposition and down-regulated the expression level of IL-1α, IL-1r1, and Cntfr as compared to the control group. Supplementation of red pitaya juice for 8 weeks increased omental and epididymal fat but no change in retroperitoneal fat was observed. Red pitaya juice reversed the changes in energy balance homeostasis in liver tissues by regulation of the expression levels of Pomc and Insr. The increased protein expression levels of IL-6 and TNF-α in HCHF group and red pitaya treated rats confirmed the results of gene expression. CONCLUSION: Collectively, this study revealed the usefulness of this diet-induced rat model and the beneficial effects of red pitaya on energy balance homeostasis by modulating the anorectic, orexigenic and energy expenditure related genes.

MicroRNA-based therapy and breast cancer: A comprehensive review of novel therapeutic strategies from diagnosis to treatment.

MicroRNAs (miRNA) are 21-23 nucleotide molecules not translated into proteins that bind and target the 3' untranslated regions of mRNA. These characteristics make them a possible tool for inhibiting protein translation. Different cellular pathways involved in cancer development, such as cellular proliferation, apoptosis, and migration, are regulated by miRNAs. The objective of this review is to discuss various miRNAs involved in breast cancer in detail as well as different therapeutic strategies from the clinic to industry. A comprehensive discussion is provided on various miRNAs involved in breast cancer development, progression, and metastasis as well as the roles, targets, and related therapeutic strategies of different miRNAs associated with breast cancer. miRNAs known to be clinically useful for the diagnosis and prognosis of breast cancer are also discussed. Different strategies and challenges, including nucleic acid-based (miRNA mimics, antagomiRs, and miRNA sponges) and drug-based (drug resistance, drugs/miRNA interaction, nanodelivery, and sensing systems) approaches to suppress specific oncogenes and/or activate target tumor suppressors are discussed. In contrast to other articles written on the same topic, this review focuses on the therapeutic and clinical value of miRNAs as well as their corresponding targets in order to explore how these strategies can overcome breast cancer, which is the second most frequent type of cancer worldwide. This review focuses on promising and validated miRNAs involved in breast cancer. In particular, two miRNAs, miR-21 and miR-34, are discussed as the most promising targets for RNA-based therapy in non-invasive and invasive breast cancer, respectively. Finally, relevant and commercialized therapeutic strategies are highlighted.

Role of fish oil in human health and possible mechanism to reduce the inflammation.

The roles of Omega-3 FAs are inflammation antagonists, while Omega-6 FAs are precursors for inflammation. The plant form of Omega-3 FAs is the short-chain α-linolenic acid, and the marine forms are the long-chain fatty acids: docosahexaenoic acid and eicosapentaenoic acid. Omega-3 FAs have unlimited usages, and they are considered as omnipotent since they may benefit heart health, improve brain function, reduce cancer risks and improve people's moods. Omega-3 FAs also have several important biological effects on a range of cellular functions that may decrease the onset of heart diseases and reduce mortality among patients with coronary heart disease, possibly by stabilizing the heart's rhythm and by reducing blood clotting. Some review studies have described the beneficial roles of Omega-3 FAs in cardiovascular diseases (CVDs), cancer, diabetes, and other conditions, including inflammation. Studies of the effect of Omega-3 FAs gathered from studies in diseased and healthy population. CVDs including atherosclerosis, coronary heart diseases, hypertension, and metabolic syndrome were the major fields of investigation. In studies of obesity, as the central obesity increased, the level of adipocyte synthesis of pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were increased and the level of anti-inflammatory adiponectin was decreased indicating a state of inflammation. The level of C reactive protein (CRP) synthesized from hepatocyte is increased by the influence of IL-6. CRP can be considered as a marker of systemic inflammation associated with increased risks of CVDs. In molecular studies, Omega-3 FAs have direct effects on reducing the inflammatory state by reducing IL-6, TNF-α, CRP and many other factors. While the appropriate dosage along with the administrative duration is not known, the scientific evidence-based recommendations for daily intake are not modified.

Molecular basis of transfusion dependent beta-thalassemia major patients in Sabah.

Beta-thalassemia is one of the most prevalent inherited diseases and a public health problem in Malaysia. Malaysia is geographically divided into West and East Malaysia. In Sabah, a state in East Malaysia, there are over 1000 estimated cases of ß-thalassemia major patients. Accurate population frequency data of the molecular basis of ß-thalassemia major are needed for planning its control in the high-risk population of Sabah. Characterization of ß-globin gene defects was done in 252 transfusion dependent ß-thalassemia patients incorporating few PCR techniques. The study demonstrates that ß-thalassemia mutations inherited are ethnically dependent. It is important to note that 86.9% of transfusion-dependent ß-thalassemia major patients in Sabah were of the indigenous population and homozygous for a single mutation. The Filipino ß(0)-deletion was a unique mutation found in the indigenous population of Sabah. Mutations common in West Malaysia were found in 11 (4.3%) patients. Four rare mutations (Hb Monroe, CD 8/9, CD 123/124/125 and IVS I-2) were also found. This study is informative on the population genetics of ß-thalassemia major in Sabah.

Effects of red pitaya juice supplementation on cardiovascular and hepatic changes in high-carbohydrate, high-fat diet-induced metabolic syndrome rats.

BACKGROUND: The fruit of Hylocereus polyrhizus, also known as red pitaya, and buah naga in Malay, is one of the tropical fruits of the cactus family, Cactaceae. Red pitaya has been shown to protect aorta from oxidative damage and improve lipid profiles in hypercholesterolemic rats probably due to phytochemicals content including phenolics and flavonoids. The aim of this study was to investigate the changes in cardiac stiffness, hepatic and renal function in high-carbohydrate, high-fat diet-induced obese rats following supplementation of red pitaya juice. METHODS: Total 48 male Wistar rats were divided into 4 groups: corn-starch group (CS), corn-starch+red pitaya juice group (CRP), high-carbohydrate, high fat group (HCHF) and high-carbohydrate, high fat+red pitaya juice (HRP). The intervention with 5% red pitaya juice was started for 8 weeks after 8 weeks initiation of the diet. Heart function was determined ex vivo with Langendorff hearts while plasma liver enzymes, uric acid and urea were measured using commercial kits. Total fat mass was determined with Dual-energy X-ray absorptiometry (DXA) scan. Glucose uptake was measured with Oral Glucose Tolerance Test (OGTT). Liver and cardiac structures were defined by histology. RESULTS: Supplementation of red pitaya juice for 8 weeks increased energy intake and abdominal circumference but no change in body fat and lean mass respectively. Also, there were a trend of uric acid and glucose normalization for HRP as compared to H-fed rats. Red pitaya juice treatment reduced ALP and ALT but caused significant increment in AST. Diastolic stiffness of the heart was reduced after supplementation of red pitaya juice in corn starch fed rats. However, the reduction was not significant in HRP rats in comparison with H rats. CONCLUSION: The present study concluded that red pitaya juice may serve as a complimentary therapy for attenuating some signs of metabolic syndrome.

Influence of conventional and ultrasonic-assisted extraction on phenolic contents, betacyanin contents, and antioxidant capacity of red dragon fruit (Hylocereus polyrhizus).

The aim of this study was to examine the effects of extraction methods on antioxidant capacities of red dragon fruit peel and flesh. Antioxidant capacities were measured using ethylenebenzothiozoline-6-sulfonic acid (ABTS) radical cation assay and ferric reducing antioxidant power assay (FRAP). Total phenolic content (TPC) was determined using Folin-Ciocalteu reagent while quantitative determination of total flavonoid content (TFC) was conducted using aluminium trichloride colorimetric method. Betacyanin content (BC) was measured by spectrophotometer. Red dragon fruit was extracted using conventional (CV) and ultrasonic-assisted extraction (UE) technique to determine the most efficient way of extracting its antioxidant components. Results indicated that UE increased TFC, reduced the extraction yield, BC, and TPC, but exhibited the strongest scavenging activity for the peel of red dragon fruit. In contrast, UE reduced BC, TFC, and scavenging activity but increased the yield for the flesh. Nonetheless, UE slightly increases TPC in flesh. Scavenging activity and reducing power were highly correlated with phenolic and flavonoid compounds. Conversely, the scavenging activity and reducing power were weakly correlated with betacyanin content. This work gives scientific evidences for the consideration of the type of extraction techniques for the peel and flesh of red dragon fruit in applied research and food industry.

Analysis of Gln223Agr polymorphism of Leptin Receptor Gene in type II diabetic mellitus subjects among Malaysians.

Leptin is known as the adipose peptide hormone. It plays an important role in the regulation of body fat and inhibits food intake by its action. Moreover, it is believed that leptin level deductions might be the cause of obesity and may play an important role in the development of Type 2 Diabetes Mellitus (T2DM), as well as in cardiovascular diseases (CVD). The Leptin Receptor (LEPR) gene and its polymorphisms have not been extensively studied in relation to the T2DM and its complications in various populations. In this study, we have determined the association of Gln223Agr loci of LEPR gene in three ethnic groups of Malaysia, namely: Malays, Chinese and Indians. A total of 284 T2DM subjects and 281 healthy individuals were recruited based on International Diabetes Federation (IDF) criteria. Genomic DNA was extracted from the buccal specimens of the subjects. The commercial polymerase chain reaction (PCR) method was carried out by proper restriction enzyme MSP I to both amplify and digest the Gln223Agr polymorphism. The p-value among the three studied races was 0.057, 0.011 and 0.095, respectively. The values such as age, WHR, FPG, HbA1C, LDL, HDL, Chol and Family History were significantly different among the subjects with Gln223Agr polymorphism of LEPR (p < 0.05).

Analysis of MTHFR and MTRR Gene Polymorphisms in Iranian Ventricular Septal Defect Subjects.

Ventricular septal defect (VSD) is one of the most common types of congenital heart defects (CHD). There are vivid multifactorial causes for VSD in which both genetic and environmental risk factors are consequential in the development of CHD. Methionine synthase reductase (MTRR) and methylenetetrahydrofolate reductase (MTHFR) are two of the key regulatory enzymes involved in the metabolic pathway of homocysteine. Genes involved in homocysteine/folate metabolism may play an important role in CHDs. In this study; we determined the association of A66G and C524T polymorphisms of the MTRR gene and C677T polymorphism of the MTHFR gene in Iranian VSD subjects. A total of 123 children with VSDs and 125 healthy children were included in this study. Genomic DNA was extracted from the buccal cells of all the subjects. The restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method was carried out to amplify the A66G and C524T polymorphism of MTRR and C677T polymorphism of MTHFR genes digested with Hinf1, Xho1 and Nde1 enzymes, respectively. The genotype frequencies of CC, CT and TT of MTRR gene among the studied cases were 43.1%, 40.7% and 16.3%, respectively, compared to 52.8%, 43.2% and 4.0%, respectively among the controls. For the MTRR A66G gene polymorphism, the genotypes frequencies of AA, AG and GG among the cases were 33.3%, 43.9% and 22.8%, respectively, while the frequencies were 49.6%, 42.4% and 8.0%, respectively, among control subjects. The frequencies for CC and CT genotypes of the MTHFR gene were 51.2% and 48.8%, respectively, in VSD patients compared to 56.8% and 43.2% respectively, in control subjects. Apart from MTHFR C677T polymorphism, significant differences were noticed (p < 0.05) in C524T and A66G polymorphisms of the MTRR gene between cases and control subjects.

Contribution of CYP2E1 polymorphism to aging in the mechanical workshop workers.

Aging is attributed to both genetic and environmental factors. Occupational exposure is one of the environmental factors with potential genotoxic effects. Researchers try to determine factors involved in genetic damages at hazards exposure that could accelerate aging. Cytochrome P450 2E1 (CYP2E1) gene contributes in activation and detoxification of the environmental hazards. This polymorphism plays an important role in susceptibility of inter-individuals to DNA damage at the occupational exposure. The current study evaluated the possible influence of this gene polymorphism in aging by genomic damages through the biomarkers alterations of micronuclei (MN), comet tail length and telomere length shortening at the exposure. In this study, buccal cells were collected from the oral cavity of exposed workers and non-exposed controls. The CYP2E1 genotypes were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The wild genotype significantly affected MN frequency (p = 0.007) and relative telomere length (p = 0.047) in the older group of workers. It was concluded that the interaction of gene polymorphism and exposure enhances DNA damage and accelerates aging consequently.

Genetic aberrations of homologous recombination repair pathways in prostate cancer: The prognostic and therapeutic implications.

Prostate cancer (PC) is the second most common cancer in men worldwide. Homologous recombination repair (HRR) gene defects have been identified in a significant proportion of metastatic castration-resistant PC (mCRPC) and are associated with an increased risk of PC and more aggressive PC. Importantly, it has been well-documented that poly ADP-ribose polymerase (PARP) inhibition in cells with HR deficiency (HRD) can cause cell death. This has been exploited for the targeted treatment of PC patients with HRD by PARP inhibitors. Moreover, it has been shown that platinum-based chemotherapy is more effective in mCRPC patients with HRR gene alterations. This review highlights the prognosis and therapeutic implications of HRR gene alterations in PC.

Association of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) Gene Polymorphisms with Type 2 Diabetes among Malay Ethnics.

Background Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, and the underlying causes remain unknown and have not been fully elucidated. Several candidate genes have been associated with T2DM in various populations with conflicting results. The variations found in glucokinase ( GCK ), glucokinase regulatory protein ( GCKR ), and glucose-6-phosphatase 2 ( G6PC2 ) genes were not well studied, particularly among Asians. Aims The main objective of this study was to determine the candidate genetic polymorphisms of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) genes in T2DM among Malay ethnics. Methods In this candidate gene association study, a total of 180 T2DM subjects and 180 control subjects were recruited to determine the genotypes using polymerase chain reaction-restriction fragment length polymorphism and Taqman probe assay methods. Genotype and allele frequencies in case and control samples were compared using the chi-squared test to determine a significant difference. Results The body mass index, fasting blood glucose, hemoglobin A1c, systolic and diastolic blood pressure, and total cholesterol were significantly different ( p < 0.05) between T2DM and control subjects. The genotypic and allelic frequencies of GCK (rs1799884), GCKR (rs780094), and G6PC2 (rs560887) gene polymorphisms were significantly different between T2DM and controls ( p < 0.05). Conclusion Hence, rs1799884 of GCK gene and rs780094 of GCKR gene and rs560887 of the G6PC2 gene are possible genetic biomarkers in T2DM development among Malay ethnics in Malaysia.

Exposure to Airborne Pesticides and Its Residue in Blood Serum of Paddy Farmers in Malaysia.

Background: Pesticides manage pests and diseases in agriculture, but they harm the health of agricultural workers. Concentrations of thirteen pesticides were determined in personal air and blood serum of 85 paddy farmers and 85 non-farmers, thereafter associated with health symptoms. Method: Samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results: The median concentration of pesticides in personal air samples ranged from 10.69 to 188.49 ng/m3 for farmers and from 5.79 to 73.66 ng/m3 for non-farmers. The median concentration of pesticides in blood serum was from 58.27 to 210.12 ng/mL for farmers and 47.83 to 62.74 ng/mL for non-farmers. Concentration of eleven pesticides in personal air and twelve pesticides in blood serum were significantly higher in farmers than non-farmers (p < 0.05). All pesticides detected in personal air correlated significantly with concentration in the blood serum of farmers (p < 0.05). Health symptoms reported by farmers were dizziness (49.4%), nausea (47.1%), cough (35.3%), chest pain (30.6%), breathing difficulty (23.5%), sore throat (22.4%), vomiting (18.8%), phlegm (16.5%), and wheezing (15.3%). Concentration of pesticides in personal air, blood serum, and health symptoms were not significantly associated. Conclusion: Occupational exposure to pesticides significantly contaminates blood serum of farmers compared to non-farmers.

Signature pattern of gene expression and signaling pathway in premature diabetic patients uncover their correlation to early age coronary heart disease.

BACKGROUND: Coronary Heart Disease (CHD) is the leading cause of death in industrialized countries. There is currently no direct relation between CHD and type 2 diabetes mellitus (T2D), one of the major modifiable risk factors for CHD. This study was carried out for genes expression profiling of T2D associated genes to identify related biological processes/es and modulated signaling pathway/s of male subjects with CHD. METHOD: the subjects were divided into four groups based on their disease, including control, type 2 diabetes mellitus (T2D), CHD, and CHD + T2D groups. The RNA was extracted from their blood, and RT2 Profiler™ PCR Array was utilized to determine gene profiling between groups. Finally, the PCR Array results were validated by using Q-RT-PCR in a more extensive and independent population. RESULT: PCR Array results revealed that the T2D and T2D + CHD groups shared 11 genes significantly up-regulated in both groups. Further analysis showed that the mRNA levels of AKT2, IL12B, IL6, IRS1, IRS2, MAPK14, and NFKB1 increased. Consequently, the mRNA levels of AQP2, FOXP3, G6PD, and PIK3R1 declined in the T2D + CHD group compared to the T2D group. Furthermore, in silico analysis indicated 36 Gene Ontology terms and 59 signaling pathways were significantly enriched in both groups, which may be a culprit in susceptibility of diabetic patients to CHD development. CONCLUSION: Finally, the results revealed six genes as a hub gene in altering various biological processes and signaling pathways. The expression trend of these identified genes might be used as potential markers and diagnostic tools for the early identification of the vulnerability of T2D patients to develop premature CHD.

A review of studies examining the association between genetic biomarkers (short tandem repeats and single-nucleotide polymorphisms) and risk of prostate cancer: the need for valid predictive biomarkers.

Prostate cancer (PCa) is a challenging polygenic disease because the genes that cause PCa remain largely elusive and are affected by several causal factors. Consequently, research continuously strives to identify a genetic marker which could be used as an indicator to predict the most vulnerable (i.e., predisposed) segments of the population to the disease or for the gene which may be directly responsible for PCa. To enhance the genetic etiology of PCa, this research sought to discover the key studies conducted in this field using data from the main journal publication search engines, as it was hoped that this could shed light on the main research findings from these studies, which in turn could assist in determining these genes or markers. From the research highlighted, the studies primarily used two kinds of markers: short tandem repeats or single-nucleotide polymorphisms. These markers were found to be quite prevalent in all the chromosomes within the research carried out. It also became apparent that the studies differed in both quantity and quality, as well as being conducted in a variety of societies. Links were also determined between the degree and strength of the relationship between these markers and the occurrence of the disease. From the studies identified, most recommended a larger and more diverse survey for the parameters which had not been studied before, as well as an increase in the size of the community (i.e., the population) being studied. This is an indication that work in this field is far from complete, and thus, current research remains committed toward finding genetic markers that can be used clinically for the diagnosis and screening of patients with PCa.

Identification of Potential Genes for Benign Prostatic Hyperplasia and Prostate Cancer Susceptibility in Four X-chromosome Regions with High Frequency of Microvariant Alleles.

BACKGROUND: The X-chromosome has been suggested to play a role in prostate cancer (PrCa) since epidemiological studies have provided evidence for an X-linked mode of inheritance for PrCa based on the higher relative risk among men who report an affected brother(s) as compared to those reporting an affected father. The aim of this study was to examine the potential association between the forensic STR markers located at four regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28 and the risk of BPH and PrCa to confirm the impact of ChrX in the PrCa incidence. This may be helpful in the incorporation of STRs genetic variation in the early detection of men population at risk of developing PrCa. METHODS: DNA samples from 92 patients and 156 healthy controls collected from two medical centers in Riyadh, Saudi Arabia were analyzed for four regions located at X-chromosome using the Investigator® Argus X-12 QS Kit. RESULTS: The results demonstrated that microvariant alleles of (DXS7132, DXS10146, HPRTB, DXS10134, and DXS10135) are overrepresented in the BPH group (p < 0.00001). Allele 28 of DXS10135 and allele 15 of DXS7423 could have a protective effect, OR 0.229 (95%CI, 0.066-0.79); and OR 0.439 (95%CI, 0.208-0.925). On the other hand, patients carrying allele 23 of DXS10079 and allele 26 of DXS10148 presented an increased risk to PrCa OR 4.714 (95%CI, 3.604-6.166). CONCLUSION: The results are in concordance with the involvement of the X chromosome in PrCa and BPH development. STR allele studies may add further information from the definition of a genetic profile of PrCa resistance or susceptibility. As TBL1, AR, LDOC1, and RPL10 genes are located at regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28, respectively, these genes could play an essential role in PrCa or BPH.

Analysis of renin-angiotensin aldosterone system gene polymorphisms in Malaysian essential hypertensive and type 2 diabetic subjects.

BACKGROUND: The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects. METHODS: RAAS gene polymorphisms were determined using mutagenically separated PCR and PCR-RFLP method in a total of 270 subjects consisting of 70 hypertensive subjects without type 2 diabetes mellitus (T2DM), 60 T2DM, 65 hypertensive subjects with T2DM and 75 control subjects. RESULTS: There was significant difference found in age, body mass index, systolic/diastolic blood pressure, fasting plasma glucose and high density lipoprotein cholesterol levels between the hypertensive subjects with or without T2DM and control subjects. No statistically significant differences between groups were found in the allele frequency and genotype distribution for A20C variant of AGT gene, MboI of renin, Gly460Trp of aldosterone and Lys173Arg of adducin (p > 0.05). However, the results for A6G of AGT gene revealed significant differences in allele and genotype frequencies in essential hypertension with or without T2DM (p < 0.001). CONCLUSION: Among the five polymorphisms of RAAS genes only A6G variant of AGT gene was significantly associated in Malaysian essential hypertensive and type 2 diabetic subjects. Therefore, A6G polymorphism of the AGT gene could be a potential genetic marker for increased susceptibility to essential hypertension with or without T2DMin Malaysian subjects.

Evaluation of Helicobacter pylori vacA genotypes in Iranian patients with peptic ulcer disease.

Helicobacter pylori is the major cause of active chronic gastritis and peptic ulcers in humans and has been linked to gastric carcinoma and lymphoma. The vacuolating cytotoxin vacA and cag pathogenicity island (cag PAI) are two identified virulence factors that are considered to have an important role in the pathogenesis of H. pylori infection. The aim of this study is to investigate the H. pylori vacA alleles in Iranian patients with peptic ulcer disease. In order to investigate this, biopsy specimens were obtained from 84 patients with gastric ulcer, gastritis, and duodenal ulcer. DNA extraction and PCR were used to detect the presence or absence of glmM, cagA and to assess the polymorphism of vacA. Of the 77 glmM PCR-positive biopsy specimens, 55 (71%) had the vacA signal sequence genotype s1, and 22 (29%) had subtype s2. vacA mid-region analysis revealed that 31 (40%) were vacA m1 and 46 (60%) were m2. The presence of the cagA gene correlated with vacA signal sequence type s1, whereas type s2 was predominantly found in cagA-negative samples (P < 0.001). Thus, the detection of vacA and cagA, virulence markers described in several clinical outcomes may be used to help the treatment and prevention of H. pylori in Iran.