Metagenomics studies for the diagnosis and treatment of prostate cancer.

AIM: Mutation occurs in the prostate cell genes, leading to abnormal prostate proliferation and ultimately cancer. Prostate cancer (PC) is one of the most common cancers amongst men, and its prevalence worldwide increases relative to men's age. About 16% of the world's cancers are the result of microbes in the human body. Impaired population balance of symbiosis microbes in the human reproductive system is linked to PC development. DISCUSSION: With the advent of metagenomics science, the genome sequence of the microbiota of the human body has been unveiled. Therefore, it is now possible to identify a higher range of microbiome changes in PC tissue via the Next Generation Technique, which will have positive consequences in personalized medicine. In this review, we intend to question the role of metagenomics studies in the diagnosis and treatment of PC. CONCLUSION: The microbial imbalance in the men's genital tract might have an effect on prostate health. Based on next-generation sequencing-generated data, Proteobacteria, Firmicutes, Actinobacteria, and Bacteriodetes are the nine frequent phyla detected in a PC sample, which might be involved in inducing mutation in the prostate cells that cause cancer.

Frequency of cystathionine beta-synthase 844INS68 polymorphism in Southern Iran.

Iranian population with an Indo-European origin is one of the oldest populations in the world. Historical evidence suggests the close similarity in the origin of Iranian, European and north Indian population. However, there are few anthropological and genetic evidences on this subject. This study, which is the first report from Iran, was performed to investigate the genetic origin of Iranian population using a polymorphism in Cystathionine beta synthase (CBS) gene known as 844INS68bp in this respect, genomic DNA was extracted from the whole blood of 480 healthy normal blood donors referred to Fars Blood Transfusion Center, using a salting out method. The fragment containing 844INS68bp was amplified, the normal fragment was 174 bp and the fragment containing the insertion was 242 bp in length. Results indicated that 418 (87.08%) out of 480 individuals had a normal (N/N) genotype, 59 (12.29%) individuals were heterozygote (N/I) and 3 (0.63%) had homozygote a mutated genotype (I/I). The total frequency of 844INS68bp allele was found 6.8% which is similar to with the reported in White Caucasians. Comparison of the genotype of this study with the polymorphism in other populations revealed that Southern Iranian population has a great similarity with other Caucasians populations' especially South Italy and North America while differed from East Asian and African populations. These results are in agreement with the result of other studied polymorphisms. Therefore, despite the great admixture of Iranian population with the neighboring non-Caucasian populations during the time, Iranian population still share a genetic background with other Caucasian populations.

Association between type 2 diabetes mellitus, biochemical factors and UCSNP-43 polymorphisms of CALPIN-10 gene in patients with atherosclerosis of coronary artery disease in Southern Iran population.

INTRODUCTION: Genetic variations in the calpain 10 gene (CALPIN-10), single nucleotide polymorphisms-43 (SNP-43), have increased the risk of type 2 diabete mellitus (T2DM) and coronary artery disease (CAD). METHODS: We studied the control and CAD groups for association of association of SNP-43 in the CALPIN-10 gene with T2DM and other risk factors of its complications. Overall, we examined 452 individuals, 224 patients with CAD and 228 healthy subjects for CAD in Iranian population. All the subjects were genotyped for the CALPIN-10, SNP-43 by polymorphism chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, using biochemical methods to detect fasting glucose and other biochemical factors in the blood sample. We assessed frequencies of SNP-43 alleles between CAD and normal population groups. RESULTS: In CAD patients, the GG allele was significantly associated with T2DM and GG allele was causing high level of glucose. But in control group, there was no relationship between them. Between clinical and biochemical risk factors with different genotypes there was no significant difference in the compared group. CONCLUSION: The results of our study suggest no significant association between SNP-43 and the risk of T2DM. In other words, CALPIN-10 did not show a major diabetes gene pool capacity in normal southern Iranian population.

Investigation of the Association Between 584C/T Polymorphism of EL Gene and Risk of Premature Coronary Artery Disease in Fars Province.

INTRODUCTION: Endothelial lipase (EL) is a protein from the triglyceride lipase family which plays an important role in high-density lipoprotein (HDL) metabolism. One of the most frequently studied variants is 584C/T which causes the amino acid threonine at codon 111 to convert to isoleucine. Many studies have shown the association of this variant with HDL-C level and CAD disease. METHODS: The population of this study consists of 140 patients (all males) with angiographically confirmed coronary artery disease (CAD) and 80 controls. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) was carried out for genotyping of LIPG 584C/T. Data were analyzed using SPSS. RESULTS: The results of the study indicated that the frequency of T allele was significantly lower among CAD patients than among controls (0.27 vs 0.36, P = .004). However, no significant correlation was found between the 584C/T variant and serum HDL-C level. Multivariate regression analysis confirmed that the T allele is significantly associated with CAD disregarding the age, hypertension, hypercholesterolemia, diabetes and HDL-C (OR = 0.494, 95% CI = 0.253- 0.968, P =.040). CONCLUSION: It was concluded that the T allele was associated with protection from CAD in Fars province independent of HDL-C level.

The Association of Lipoprotein Lipase Genes, HindIII and S447X Polymorphisms With Coronary Artery Disease in Shiraz City.

INTRODUCTION: Several polymorphisms at the lipoprotein lipase (LPL) locus are associated with variations in LPL activity serum lipid concentrations and the risk of coronary artery disease (CAD). The aim of this study was to investigate the role of the LPL S447X and HindIII polymorphism in a sample of subjects with CAD and compare them with healthy subjects. METHODS: The study enrolled 115 patients and 89 healthy subjects who were recruited from Namazi hospital in 2010-2012. The presence of two common polymorphisms of the LPL gene (HindIII and S447X) was determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis using genomic DNA. SPSS 16.0 was used for statistical analysis. RESULTS: S447X was significantly different between the patients with CAD and the healthy subjects (P < 0.001). But HindIII was not significantly different between the patients with CAD and the healthy subjects (P = 0.741). Risk factors such as smoking, hypertension, hyperlipidemia, triglyceride (TG) and high-density lipoprotein (HDL) levels had a significant association with CAD. CONCLUSION: In our study, the presence of G allele S447X polymorphism increases the TG level and decrease HDL level, so it increases the susceptibility CAD. Moreover, HindIII polymorphism did not have any significant association with CAD.

Non-modifiable Factors of Coronary Artery Stenosis in Late Onset Patients with Coronary Artery Disease in Southern Iranian Population.

INTRODUCTION: Coronary Artery disease (CAD) is influenced by genetic factors, environment and culture behavior. The aim of the present study was to evaluate some non-modifiable risk factors of coronary heart disease such as sex, age, family history and consanguineous marriage. METHODS: This is a case-control study. The study population consisted of 200 fifteen or more years old. Data were collected on 200 patients with positive angiography and 200 control subjects with negative angiography. Positive angiography was defined as coronary diameter cut greater than 50%. Statistical analysis was conducted using SPSS 11.5. In this study, data were collected through a checklist. Logistic regression and stratification were used to determine the impact of age, gender, family history, and consanguinity on the risk of stenosis. RESULTS: The percentage of men in patients and controls were 89% and 29%, respectively. As to gender, a significant association was found between patients and controls of CAD (CI 95%, 4.014-10.052, OR 6.352). Gender was determined as a risk factor for CAD. Family history of myocardial infarction did not show a significant effect on the artery stenosis. As to consanguinity of the parents, there was no significant association between patients and controls of CAD (P> 0.05). CONCLUSION: These researches show that ageing increases the risk of coronary heart stenosis; also, females are more than men protected against this disease. The impact of family history of myocardial infarction and consanguineous marriage were not associated with of CAD.

An MTHFR variant, plasma homocysteine levels and late-onset coronary artery disease in subjects from southern Iran.

There have been many controversial debates on the role of Hyperhomocysteinaemia (HHcy) as an independent risk factor for Coronary Artery Disease (CAD) during recent years. Furthermore, an alanine/valine (Ala/Val) gene polymorphism at 222nd amino acid of 5,10-methylenetetrahydrofolate reductase (MTHFR) has been considered as a factor that could render this enzyme thermolabile and less active which in turn may yield a subsequent increase in plasma total homocysteine (tHcy) levels. To assess whether this polymorphism is associated with increased risk of CAD and plasma levels of tHcy in a population from southern Iran, a total of 457 patients with angiographically documented multi-vessel CAD were compared with a control group comprised of 371 subjects with <30% stenosis in all major vessels. Nevertheless our results failed to admit a significant difference between CAD individuals and control subjects for Ala/Val polymorphism and plasma Hcy concentrations. However, plasma Hcy concentrations were significantly higher in individuals with Val/Val genotype than subjects with Ala/Ala genotype, but it didn't show a significant association with CAD in our population. Moreover, as the multiple linear regression analysis indicated, smoking habit, folate levels and the MTHFR Val/Val genotype were the only major predictors of tHcy concentrations in the current investigation.

5,10-methylene tetrahydrofolate reductase C677T gene polymorphism, homocysteine concentration and the extent of premature coronary artery disease in southern Iran.

Elevated level of plasma homocysteine (Hcy) has been identified as an independent risk factor for coronary artery disease (CAD). Furthermore, numerous studies have documented the influences of a common polymorphism (C677T) of methylenetetrahydrofolate reductase (MTHFR) on homocysteine levels. However the relationship between this mutation and cardiovascular diseases (CVD) has remained as a controversial issue. The present study was undertaken to investigate the relationship between C677T polymorphism of MTHFR gene, plasma total Hcy levels and the number of affected vessels as a criterion for the extent of CAD. MTHFR genotypes and plasma homocysteine (HCY) concentrations were examined in 231 patients and 300 healthy subjects who underwent diagnostic coronary angiography. A multiple linear regression analysis was performed to identify the predictors of Hcy levels whereas logistic regression model was built to determine the association of Hcy quartiles with the risk of CAD adjusted for risk factors. The prevalence of MTHFR genotypes was similar between CAD patients and non-CAD individuals while the geometric mean of Hcy values was significantly higher in patient group (14.13 ± 4.11 µmol/l) than in control group (10.19 ± 3.52 µmol/l) (P < 0.001). Moreover, unlike the MTHFR polymorphism, Hcy concentration increased with increasing number of stenosed vessels and the CAD risk increased about 2 folds in the top two Hcy quartiles (≥ 17.03 and 13.20-17.02 µmol/l) compared with the lowest quartile (≤ 9.92 µmol/l) after controlling for conventional risk factors (P<0.001 for both). Our data suggest that hyperhomocysteinaemia (HHcy) is significantly associated to CAD risk increase as well as to the extent of coronary atherosclerosis.

Lack of association between Ser(413)/Cys polymorphism of plasminogen activator inhibitor type 2 (PAI-2) and premature coronary atherosclerotic disease.

Plasminogen activator inhibitor type-2 (PAI-2) is a serine protease inhibitor of the fibrinolytic system produced predominantly by the macrophages and monocytes. It has been demonstrated that fibrinolysis regulation has a great importance in the pathogenesis of atherosclerotic plaques. Thus in the current investigation, we sought to determine whether Ser(413)/Cys polymorphism (rs6104) of PAI-2 gene could be associated with atherosclerosis and cardiovascular risk factors. Ser(413)/Cys polymorphism was determined by PCR-RFLP technique using Mwo I restriction enzyme for 184 men under 50 years of age and 216 women less than 55 years of age who underwent diagnostic coronary angiography. Data on the history of familial myocardial infarction or other heart diseases, hypertension, and smoking habit were collected by a simple questionnaire. Fasting levels of blood sugar, triglycerides, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol levels were also measured by enzymatic methods. Frequencies of the Ser(413) and Cys(413) alleles were 0.760 and 0.240 in the whole population, respectively. The PAI-2 gene variant analyzed was not significantly associated with either the prevalence of premature CAD or the classical risk factors of CAD development such as diabetes, serum cholesterol, triglycerides, low-density lipoprotein and high-density lipoprotein cholesterol, body mass index, hypertension, familial history of heart dysfunction or smoking.

Sex chromosome aneuploidy in cytogenetic findings of referral patients from south of Iran.

BACKGROUND: Chromosome abnormality (CA) including Sex chromosomes abnormality (SCAs) is one of the most important causes of disordered sexual development and infertility. SCAs formed by numerical or structural alteration in X and Y chromosomes, are the most frequently CA encountered at both prenatal diagnosis and at birth. OBJECTIVE: This study describes cytogenetic findings of cases suspected with CA referred for cytogenetic study. MATERIALS AND METHODS: Blood samples of 4151 patients referred for cytogenetic analysis were cultured for chromosome preparation. Karyotypes were prepared for all samples and G-Banded chromosomes were analyzed using x100 objective lens. Sex chromosome aneuploidy cases were analyzed and categorized in two groups of Turners and Klinefelter's syndrome (KFS). RESULTS: Out of 230 (5.54%) cases with chromosomally abnormal karyotype, 122 (30%) cases suspected of sexual disorder showed SCA including 46% Turner's syndrome, 46% KFS and the remaining other sex chromosome abnormalities. The frequency of classic and mosaic form of Turner's syndrome was 33% and 67%, this was 55% and 45% for KFS, respectively. CONCLUSION: This study shows a relatively high sex chromosome abnormality in this region and provides cytogenetic data to assist clinicians and genetic counselors to determine the priority of requesting cytogenetic study. Differences between results from various reports can be due to different genetic background or ethnicity.

Apolipoprotein E polymorphism in Southern Iran: E4 allele in the lowest reported amounts.

BACKGROUND: Apolipoprotein E (apoE) with three major alleles E2, E3 and E4 is one of the critical genes in lipid metabolism. Common apoE alleles are in association with an increase in risk for central nervous and cardiovascular diseases such as Alzheimer's disease, dementia, multiple sclerosis, atherosclerosis, coronary heart disease, hyperlipoproteinemia and stroke. ApoE3 is known as the most frequent allele in all populations, while association of apoE gene polymorphism with reported diseases have mostly been related to other two major alleles especially apoE4. OBJECTIVE: To determine of apoE alleles frequencies in Southern Iran and comparison of those frequencies with other populations. METHODS: DNA was extracted from the whole blood of 198 healthy unrelated candidates from population of Fars Province, Southern Iran, for apoE genotyping who were checked up by a physician. The frequencies of apoE alleles were compared with other populations by chi(2) test. RESULTS: The frequencies of E2, E3 and E4 were 0.063, 0.886 and 0.051 respectively. These values were similar to those reported from populations of Kuwait, Oman, Lebanon, India, Turkey, Greece, Spain, Sardinia Islands of Italy and two Iranian populations but were different from South of Italy and Caucasians in other Europe regions, American, American-Indian, African, East Asian and Saudi populations (P < 0.05). CONCLUSION: The frequency of E4 allele as a genetic risk factor for some multifactorial diseases in the population of Southern Iran is in the lowest reported amounts in the world. Iranian population has Caucasoid origin but differs from some Caucasian populations in Europe and America. The results of present study are in agreement with the historical evidences which show admixture of Iranian population with other populations and some studies based on genetic polymorphisms in the population of Southern Iran.