Contribution of genetic variants in the development of familial premature coronary artery disease in a cohort of cardiac patients.

Coronary artery disease (CAD), the most prevalent cardiovascular disease, is the leading cause of death worldwide. Heritable factors play a significant role in the pathogenesis of CAD. It has been proposed that approximately one-third of patients with CAD have a positive family history, and individuals with such history are at ~1.5-fold increased risk of CAD in their lifespans. Accordingly, the long-recognized familial clustering of CAD is a strong risk factor for this disease. Our study aimed to identify candidate genetic variants contributing to CAD by studying a cohort of 60 large Iranian families with at least two members in different generations afflicted with premature CAD (PCAD), defined as established disease at ≤45 years in men and ≤55 years in women. Exome sequencing was performed for a subset of the affected individuals, followed by prioritization and Sanger sequencing of candidate variants in all available family members. Subsequently, apparently healthy carriers of potential risk variants underwent coronary computed tomography angiography (CCTA), followed by co-segregation analysis of the combined data. Putative causal variants were identified in seven genes, ABCG8, CD36, CYP27A1, PIK3C2G, RASSF9, RYR2, and ZFYVE21, co-segregating with familial PCAD in seven unrelated families. Among these, PIK3C2G, RASSF9, and ZFYVE21 are novel candidate CAD susceptibility genes. Our findings indicate that rare variants in genes identified in this study are involved in CAD development.

Factor V Leiden but not the factor II 20210G>A mutation is a risk factor for premature coronary artery disease: a case-control study in Iran.

Background: Factor V Leiden (FVL) and factor II c.∗97G>A (rs1799963) are genetic risk factors for venous thromboembolism. Their contribution to coronary artery disease (CAD) is less clear. Objectives: This study aimed to investigate the association between FVL, rs1799963, and premature CAD in Iranians. Methods: We performed a genetic case-control study of 944 cases and 1081 controls from the premature CAD Milano-Iran study, including patients aged 18-55 (female) and 18-45 years (male) who underwent coronary angiography at the Tehran Heart Centre (Iran) in 2004-2011. Cases had luminal stenosis ≥50% in at least 1 main coronary artery or branch. Controls were age- and sex-matched with no CAD history. FVL and rs1799963 were genotyped using TaqMan SNP genotyping assays. Association was tested by logistic regression adjusted for matching factors and ethnicity. Effect modification by sex and cardiovascular risk factors (metabolic [obesity, hypertension, hyperlipidemia, and diabetes], and smoking) was assessed. Results: The risk of premature CAD was increased by 50% in FVL carriers (adjusted odds ratio [adjOR] 1.54 [95% CI, 0.95-2.48]) and slightly reduced in rs1799963 carriers (adjOR 0.71 [95% CI, 0.40-1.27]). These effects were more pronounced in women than men (FVL, adjOR 1.66 vs 1.25; rs1799963, adjOR 0.60 vs 1.07). The risk of premature CAD was substantially increased in carriers of FVL with at least 1 metabolic risk factor compared with noncarriers without metabolic risk factors (adjOR 25.14 [95% CI, 12.51-50.52]). Conclusion: FVL but not FII rs1799963 was associated with an increased risk of CAD in young Iranians. This risk increased considerably when combined with metabolic cardiovascular risk factors.

Analysis of carbapenemases genes of carbapenem-resistant Klebsiella pneumoniae isolated from Tehran heart center.

Background and Objectives: Emerging of carbapenem-resistant Klebsiella pneumoniae (CRKP) is one of the major concerns among healthcare systems. This study aimed to investigate the antibiotic susceptibility pattern and carbapenemase genes of carbapenemase-producing K. pneumoniae isolates obtained from Iranian hospitalized patients. Materials and Methods: This study was performed on 71 CRKP strains isolated from different clinical specimens collected in Tehran Heart Center (Tehran, Iran). A Modified Hodge test (MHT) was done for the detection of carbapenemase-producing K. pneumoniae. The presence of bla KPC, bla VIM, bla IMP, bla NDM, and bla OXA-48 -type carbapenemases was evaluated by the PCR method. Results: We identified 8.82% (71/805) of K. pneumoniae isolates as CRKP by MHT test. The antibiotic susceptibility indicated that all isolates were resistant to imipenem, meropenem, cefotaxime, ceftazidime, cefepime, ceftriaxone, cephalothin, ciprofloxacin, and augmentin, and then mostly resistant to aztreonam, cefoxitin, gentamicin, and trimethoprim/sulfamethoxazole with 98.6%, 98.6%, 97.2%, and 94.4%, respectively. The lowest resistance was related to amikacin with 46.5% (33/71 isolates). The level of imipenem MIC for all carbapenem-resistant isolates was estimated ≥32 µg/mL. Among positive isolates for carbapenemase genes, the most frequent gene was bla OXA-48. It was found in 48 (67.6%) isolates followed by bla VIM in 28 (39.4%) isolates. bla IMP, bla NDM, and bla KPC genes were identified in 19 (26.8%), 13 (18.3%) and 5 (7.0%) isolates, respectively. These genes were not detected in nine isolates. Conclusion: The relatively high frequency of some carbapenemase genes suggests major concern about the emergence of isolates containing carbapenem resistance genes as a potential health threat.

Association between rs3088440 (G > A) polymorphism at 9p21.3 locus with the occurrence and severity of coronary artery disease in an Iranian population.

BACKGROUND: Several genome-wide association studies showed that a series of genetic variants located at the chromosome 9p21 locus are strongly associated with coronary artery disease (CAD). RATIONALE AND PURPOSE OF THE STUDY: In the present study, the relationship of rs3088440 (G > A) in cyclin-dependent kinase inhibitor 2A (CDKN2A) gene site with the presence of coronary artery disease (CAD) and its severity was evaluated in an Iranian population. METHODS AND RESULTS: The presence of rs3088440 (G > A) genotypes was assessed by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique in 324 CAD patients and 148 normal controls. rs3088440 (G > A) polymorphism was associated with increased risk of CAD in the total population (adjusted OR = 1.76, 95% CI = 1.10-2.82; p-value = 0.017) or in women (adjusted OR = 2.96, 95% CI = 1.34-6.55; p-value = 0.007), but not in the men (adjusted OR = 1.35, 95% CI = 0.70-2.6; p-value = 0.368). CONCLUSIONS: Our findings suggest that the presence of rs3088440 (G > A) is potentially linked with the risk of CAD and its severity in whole study subjects or in women only, independent of CAD risk factors.

Predictive Inflammation-related microRNAs for Cardiovascular Events Following Early-Onset Coronary Artery Disease.

BACKGROUND: Early-onset coronary artery disease (EOCAD) increases the risk of major cardiac adverse events (MACE) at the level of safety/effectiveness-related events. Since adverse events affect the quality of life of young patients with EOCAD, MACE prediction is of great importance for improving medical decision-making. AIMS OF THE STUDY: We sought to determine whether the most important inflammation-related microRNAs in atherogenesis could predict MACE among patients with EOCAD. METHODS: This nested case-control study recruited 143 young patients (males ≤45 and females ≤55 years old), selected from a cohort of patients with premature coronary atherosclerosis at a median follow-up period of 64.1 months. Total RNAs were extracted from their peripheral blood mononuclear cells. The expression levels of 18 miRNAs, which are involved in inflammation and atherogenesis, were analyzed via quantitative reverse transcription PCR. RESULTS: A scoring model based on the upregulation of miR-146a_1 and miR-342_1, along with a history of myocardial infarction and the chronic usage of antithrombotic drugs, was able to predict MI/death at the level of safety-related events (higher vs lower risk scores: sHR: 4.61, 95% CI: 1.57-13.57, and p = 0.005). Another prediction model based on the downregulation of miR-145_1, age, and a history of unstable angina was also able to predict revascularization at the level of effectiveness-related events (higher vs lower risk scores: sHR: 2.90, 95% CI: 1.49-5.66, and p = 0.002). CONCLUSIONS: Our results highlighted the role of miRNAs in adverse cardiac events and suggest that miR-146a_1, miR-342_1, and miR-145_1 may be useful biomarkers in predictive and preventive cardiology.

The association between CYBA gene C242T variant and risk of metabolic syndrome.

BACKGROUND: Both inflammation and oxidative stress may contribute to pathogenesis of metabolic syndrome (MetS). The C242T polymorphism (rs4673) in the CYBA gene, as the main components of NAD (P) H oxidase, causes inter-individual variability in the enzyme activity. We aimed to investigate the association between this polymorphism with MetS and its components. METHODS: Two hundred nine patients with MetS and 232 controls were included in this study. MetS was defined based on NCEP ATP-III A criteria with some modifications. The C242T polymorphism within CYBA gene was determined by using PCR-based restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: After applying a multiple logistic regression model with adjusting for potential confounders of MetS including, age, sex, body mass index, hypertension, used medications, and diabetes mellitus, C242T polymorphism was found to be associated with the presence of MetS in men but not in the total population or in women. T allele as compared to C allele was associated with decreased odds of MetS in men (adjusted OR = 0.42, 95% CI = 0.24-0.74; P = .003), but not in women (adjusted OR = 1.03, 95% CI = 0.07-1.61; P = .890), or in the total population (adjusted OR = 0.72, 95% CI = 0.51-1.02; P = .063). CONCLUSION: This study shows that T allele of C242T polymorphism in CYBA gene is protective against MetS in Iranian men but not in women. Further cohort studies with larger sample size in subgroups of men and women are required to confirm such association in other racial or ethnic group.

Association between polymorphisms in microRNA seed region and warfarin stable dose.

BACKGROUND: The optimal dose of anticoagulant warfarin varies among patients to achieve the target international normalised ratio. Although genetic variations related to warfarin pharmacokinetics and vitamin K cycle are important factors associated with warfarin dose requirements, these variations do not completely explain the large interindividual variability observed in the most populations, suggesting that additional factors may contribute to this variability. microRNAs have recently been introduced as regulators of drug function genes, and therefore, may be involved in drug responses. In this study, we aimed to evaluate the possible association between variants in the seed region of microRNAs, which target the genes involved in the action of warfarin and warfarin dose requirement. METHODS: 526 samples were collected from Iranian patients. Four selected polymorphisms in the seed region of microRNAs (rs2910164, rs66683138, rs12416605 and rs35770269 in miR-146a, miR-3622a, miR-938 and miR-449c, respectively) were genotyped by PCR-restriction fragment length polymorphism method. RESULTS: rs2910164 C/G in the seed region of miR-146a was associated with warfarin dose requirement (p<0.001); the patients with GG genotype had the higher mean dose of warfarin (40.6 mg/week, compared with 33.9 and 31.8 mg/week for GC and CC genotypes, respectively). The association of other polymorphisms with warfarin dose requirement was not statistically significant. CONCLUSION: rs2910164 C/G in the seed region of miR-146a is associated with warfarin maintenance dose, likely by disrupting interaction between miR-146a and ATP-binding cassette subfamily B member 1 gene, ABCB1. Therefore, this polymorphism may possibly be a potential factor for assessment of warfarin dose requirements.

Association between four microRNA binding site-related polymorphisms and the risk of warfarin-induced bleeding complications.

Bleeding is the most serious complication of warfarin anticoagulation therapy and is known to occur even at patients with therapeutic international normalized ratio (INR) range. Recently, it has been shown that microRNAs play a significant role in pharmacogenetics by regulating genes that are critical for drug function. Interaction between microRNAs and these target genes could be affected by single-nucleotide polymorphisms (SNPs) located in microRNA-binding sites. This study focused on 3'-untranslated region (3'-UTR) SNPs of the genes involved in the warfarin action and the occurrence of bleeding complications in an Iranian population receiving warfarin. A total of 526 patients under warfarin anticoagulation therapy with responding to the therapeutic dose and maintenance of the INR in the range of 2.0-3.5 in three consecutive blood tests were included in the study. Four selected 3'-UTR SNPs (rs12458, rs7294, rs1868774 and rs34669593 located in GATA4, VKORC1, CALU and GGCX genes, respectively) with the potential to disrupt/eliminate or enhance/create microRNA-binding site were genotyped using a simple PCR-based restriction fragment length polymorphism (PCR-RFLP) method. Patients with the rs12458 AT or TT genotypes of the GATA4 gene had a lower risk of bleeding compared to patients with the AA genotype (adjusted OR: 0.478, 95% CI: 0.285-0.802, P= 0.005, OR: 0.416, 95% CI: 0.192-0.902, P= 0.026, respectively). 3'-UTR polymorphisms in other genes were not significantly associated with the risk of bleeding complications. In conclusion, the SNP rs12458A>T in the 3'UTR region of GATA4 is associated with the incidence of warfarin-related bleeding at target range of INR, likely by altering microRNA binding and warfarin metabolism. Further genetics association studies are needed to validate these findings before they can be implemented in clinical settings.

Prothrombin Gene G20210A Variant in Angiographically Documented Patients with Coronary Artery Stenosis.

Background: Studies on the association between the prothrombin G20210A variant and coronary artery disease (CAD) risk are inconclusive. This study aimed to investigate the possible association between the G20210A variant in the prothrombin gene and documented CAD and its severity. Methods: This study enrolled 1460 patients who were consecutively admitted for elective coronary angiography. Via the standard angiographic techniques, coronary angiographies were done and the presence and severity of CAD were determined through the clinical vessel score and the Gensini score. Prothrombin G20210A genotypes were identified using PCR-RFLP. Results: This cross-sectional study was performed on 953 men and 507 women at a mean age of 58.21±10.33 years. The median and the interquartile range for the Gensini score were not statistically significantly different between the wild (GG) and mutant (AA+GA) genotypes (P=0.440). The association between the G20210A polymorphism and the severity of CAD with respect to the vessel score also showed no significant linear trend of higher numbers of diseased vessels (P= 0.765 for the Mantel-Haenszel test of linear trend) in the AA+GA genotype as compared with the GG genotype. Conclusion: Our data failed to confirm the hypothesis that the G20210A variant mutation may be a significant determinant of CAD risk or its severity.

Normal Reference Interval of WBC Count After On - Pump Coronary Artery Bypass Graft; When Values Could Be Misleading.

BACKGROUND: Applying the cardiopulmonary pump produces inflammatory responses and induces leukocytosis. White Blood Cell (WBC) count has a diagnostic value for detecting different infections. In this study, we want to redefine the normal value reference intervals of WBC count in Coronary Artery Bypass Graft (CABG) patients, to prevent misdiagnose leukocytosis as a sign of infection. METHODS: In an observational study, 140 patients who underwent on - pump CABG were enrolled to find out normal values of the reference interval. WBC counts were evaluated for all of them one day before the operation, first 30 minutes of ICU entrance, after 24 hours, and 48 hours after operation. Normal values of reference intervals were calculated for each measurement by two different statistical methods. RESULTS: There were 102 men and 38 women with age average of 61 years. There was no significant difference between genders' WBC counts before operation (P = 0.151), ICU entrance (P = 0.391), 24 hours after surgery (P = 0.698), and 48 hours after surgery (P = 0.523). The mean values of WBC after surgery were higher than the normal range of reference interval and had an increasing trend in the first 48 hours after surgery. The WBC values were significantly different between pre and post operation (before operation and ICU admission (P = 0.001), ICU admission and 24 hours later (P = 0.001), 24 hours after surgery, and 48 hours after surgery (P = 0.001)). All post - operative reference values were significantly higher than the range for the general population. CONCLUSIONS: There is a significant increase in WBC count after on - pump CABG. The normal range of WBC should be revised and adjusted to prevent misinterpretation as a sign of infection.

Complementary Diagnostic Value of Heart Type Fatty Acid-binding Protein in Early Detection of Acute Myocardial Infarction.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a novel biomarker for myocardial injury. We compared the use of H-FABP with serum levels of cardiac troponin-T (cTnT) and creatine kinase-MB (CK-MB) in the diagnosis of patients suspicious to acute myocardial infarction (AMI). METHODS: From October 2013 to December 2014, 182 consecutive patients suspicious to acute coronary syndrome were enrolled in this study, who presented within the past 6 hours from the onset of symptoms. Venous blood samples were drawn at baseline to measure serum biochemistry, high-sensitive cardiac troponin T (hs-cTNT), creatine kinase-MB, and H-FABP, and the measurements were repeated after 8 hours. The patients were categorized into 3 groups based on the baseline and second measurements of cTnT and general characteristics, and changes of H-FABP levels were then compared between the groups. Sensitivity and specificity of H-FABP in predicting the presence of AMI was calculated. RESULTS: A total of 91 patients had AMI. Changes of H-FABP through time were also significantly different between the AMI and non-AMI patients (P < 0.001). A cutoff point of 7.15 for H-FABP could predict AMI with a sensitivity of 51.5%, specificity of 96.3%, and diagnostic accuracy of 68.3%. The area under the receiver operating characteristic curve for H-FABP at 8 hours was 79.4% (95% confidence interval: 73.0-85.9; P < 0.001). Positive predictive value and negative predictive value for H-FABP were 85% and 60%, respectively. CONCLUSIONS: H-FABP can be used as an additional cardiac biomarker in the diagnosis of AMI.

Association between the Hepatic Lipase Promoter Region Polymorphism (-514 C/T) and the Presence and Severity of Premature Coronary Artery Disease.

Background: Hepatic lipase (HL) plays a crucial role in lipid metabolism, but there is debate about whether HL acts in a more pro- or more anti-atherogenic fashion. We aimed to examine the relationship between the -514 C/T polymorphism within the HL gene (LIPC) and the risk of angiographically determined premature coronary artery disease (CAD). Methods: Four hundred seventy-one patients with newly diagnosed angiographically documented (≥ 50% luminal stenosis of any coronary vessel) premature CAD were compared to 503 controls (subjects with no luminal stenosis in coronary arteries). A real-time polymerase chain reaction and high-resolution melting analysis was used to distinguish between the genotypes. Results: There was no significant difference in the distribution of -514 C/T genotypes between the 2 groups in the whole population or in the men, but the examined polymorphism was found to be associated with the presence of CAD in the women (p value = 0.029). After the application of a multiple logistic regression model, the minor T allele of the LIPC gene was not found to be independently associated with the presence of CAD either in the total population (adjusted OR = 0.97, 95% CI = 0.75-1.25; p value = 0.807) or in the women (adjusted OR = 0.91, 95% CI = 0.59-1.40; p value = 0.650) and in the men (adjusted OR = 1.15, 95% CI = 0.81-1.64; p value = 0.437) separately. Conclusion: Our findings suggest that there is no relationship between the LIPC -514 C/T and the risk of premature CAD or its severity in patients undergoing coronary angiography.

C1019T Polymorphism in the Connexin 37 Gene and Myocardial Infarction Risk in Premature Coronary Artery Disease.

Background: The C1019T polymorphism of the connexin-37 (GJA4) gene is a single-nucleotide polymorphisms involved in atherosclerotic plaque rupture and atherosclerosis predisposition. We examined the association between the C1019T polymorphism of the GJA4 gene and the occurrence of myocardial infarction (MI) in patients with premature coronary artery disease (CAD). Methods: Our study recruited 1000 patients with the final diagnosis of premature CAD and classified them into 2 groups: with a history of MI (n = 461) and without it (n = 539). The polymorphism variants were determined via the PCR-RFLP, and then genotyping was conducted through the high-resolution melting method. From a total of 1000 patients, 554 patients, who had been previously followed-up with a median follow-up time of 45.74 months vis-à-vis long-term major adverse cardiac events, were enrolled in this retrospective cohort phase. Results: The frequencies of the wild, heterozygous, and mutant genotypes of the C1019T polymorphism were 54.0%, 40.6%, and 5.4% in the MI group and 49.2%, 43.2%, and 7.6% in the non-MI group (p value = 0.187). After adjustment for the baseline covariates, no difference was found between the MI and non-MI groups apropos the frequency of the heterozygous genotype (p value = 0.625) and the mutant genotype (p value = 0.452). Regarding the level of human connexin-37, the serum level of this marker was not different between the MI and non-MI groups. Conclusion: The C1019T polymorphism of the GJA4 gene may not be useful for predicting the occurrence of MI in patients with premature CAD. The presence of this polymorphism in such patients may also have a low value for predicting long-term CAD complications.

NQO1 C609T Polymorphism is Associated with Coronary Artery Disease in a Gender-Dependent Manner.

Findings on the association of NQO1 C609T polymorphism in the NQO1 gene and cardiovascular disease susceptibility are controversial. The objective of the current study was to examine the relationship between this polymorphism and the presence and severity of angiographically determined coronary artery disease (CAD). One-hundred and forty-five patients with newly diagnosed angiographically documented CAD (≥50 % luminal stenosis of any coronary vessel) as case group were compared to 139 controls (subjects with no luminal stenosis at coronary arteries). The presence of C609T polymorphism was analyzed using polymerase chain reaction-based restriction fragment length polymorphism. Among total population, those with combined CT/TT (T allele carrier) genotype showed a trend toward lower odds of CAD compared to those with CC (wild type) genotype, but it did not reach a statistically significant level (p = 0.061). When data were analyzed separately for men or women, CT + TT group as compared to CC genotype was associated with decreased odds of CAD in women (adjusted OR 0.4, 95 % CI 0.2-0.9; p = 0.043), but not in men (adjusted OR 0.8, 95 % CI 0.3-1.9; p = 0.612). The C609T polymorphism within NQO1 is independently associated with CAD in women, but no association was observed in whole study population or in men.

Analyzing Gensini Score as a Semi-Continuous Outcome.

Background: Investigators frequently encounter continuous outcomes with plenty of values clumped at zero called semi-continuous outcomes. The Gensini score, one of the most widely used scoring systems for expressing coronary angiographic results, is of this type. The aim of this study was to apply two statistical approaches based on the categorization and original scale of the Gensini score to simultaneously assess the association between covariates and the presence and severity of coronary artery disease (CAD). Methods: We considered the data on 1594 individuals admitted to Tehran Heart Center with CAD symptoms from July 2004 to February 2008. The participants' baseline demographic and clinical characteristics were collected, and their coronary angiographic results were expressed through the Gensini score. The generalized ordinal threshold and two-part models were applied for the statistical analyses. Results: Totally, 320 (20.1%) individuals had a Gensini score of zero. The results of neither the two-part model nor the generalized ordinal threshold model showed a significant association between Factor V Leiden and the occurrence of CAD. However, based on the two-part model, Factor V Leiden was associated with the severity of CAD, such that the Gensini score increased by moving from a wild genotype to a heterozygote (ß = 0.44; 95% CI: 0.20-0.69 in logarithm scale) or a homozygote mutant (ß = 0.70; 95% CI: 0.28- 1.12 in logarithm scale). The proportional odds assumption was not met in our data ([Formula: see text]= 54.26; p value < 0.001); however, a trend toward severe CAD was also observed at each category of the Gensini score using the generalized ordinal threshold model. Conclusion: We conclude that besides loss of information by sorting a semi-continuous outcome, violation from the proportional odds assumption complicates the final decision, especially for clinicians. Therefore, more straightforward models such as the two-part model should receive more attention while analyzing such outcomes.

Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR).

BACKGROUND: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. METHODS: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0-3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P=0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P=0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. CONCLUSION: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations.

Correlation Between qacE and qacE∆1 Efflux Pump Genes, Antibiotic and Disinfectant Resistant Among Clinical Isolates of E.coli.

INTRODUCTION: Antiseptics and disinfectants have been used widely in hospitals and other health care settings to control the growth of microorganisms. However, some disinfectant resistant strains were reported. The objectives of our study were to evaluate correlation between the efflux pump genes, drugs and disinfectant resistant among clinical isolates of E.coli. METHODS: A total of 102 of E. coli strains were isolated from urine sample of hospitalized patients. The antibiotic susceptibility was carried out by disc diffusion method. Didecyl di-methyl ammonium chloride (DDDMAC) was used as Quaternary ammonium compound (QAC) disinfectant which was used in Heart Center Hospital. PCR reaction was carried out for detection of qacE and qac∆E efflux pump genes. RESULT: Almost all the strains had higher resistance to ampicillin, ciproflaxacin, cotrimaxazole and cephalothin. Totally 49% (n: 50) of strains were produced ESBL. Almost all the strains have MIC value between 0.00195 to 0.0078 mg/l for DDDMAC. Correlation between presence of qacE and qac∆E genes and antibiotic resistance was perceived. Presence of qacE and qac∆E genes among strains that have high disinfectant MIC value were 96.9% and 93.7% respectively. In addition, 98% of ESBL producing strains harbored qacE gene and 94% of ESBL producing strains harbored qac∆E gene. CONCLUSION: Our study indicated that there was a strong correlation between presence of qacE and qac∆E genes with resistance to some antibiotics and growth in media which contain high concentration of disinfectant. In conclusion, other mechanisms also play important role in resistant to antimicrobial agents but the role of efflux pumps in resistant to antimicrobial agents should not be neglected.

Association of KALRN, ADIPOQ, and FTO gene polymorphism in type 2 diabetic patients with coronary artery disease: possible predisposing markers.

OBJECTIVES: Recently, several genes have been introduced as potential genetic markers for diabetes mellitus and coronary artery diseases (CAD). METHODS: In this case-control study, the associations of rs2241766 T/G of ADIPOQ, rs9289231 T/G of KALRN, and rs9939609 A/T of FTO polymorphisms with genetic susceptibility to CAD in type 2 diabetic (T2D) patients were investigated. A total of 224 T2D patients undergoing coronary angiography were randomly recruited into the study. Of the total diabetic patients, 152 were also diagnosed with CAD, whereas the rest were control participants. Genotyping of single-nucleotide polymorphisms was performed by high-resolution melting analysis. RESULTS: Genotype analysis showed that the minor allele (G) frequency of rs2241766 ADIPOQ was statistically significant in the CAD group compared with the control group [odds ratio (OR), 2.779; 95% confidence interval (CI), 1.403-5.504; P=0.003]. Also, it was found that the minor allele (G) frequency of rs9289231 KALRN was significantly associated with the risk of CAD (OR, 2.098; 95% CI, 1.096-4.017; P=0.025). In addition, no significant association was observed between the minor allele (A) of the FTO rs9939609 polymorphism and CAD (OR, 1.088; 95% CI, 0.578-2.015; P=0.788). It is speculated that the GG genotype and the G allele of the rs9289231 polymorphism of KALRN and the rs224766 polymorphism of ADIPOQ genes may be considered genetic risk factors for CAD in T2D patients and genetic variations of these genes may play a major role in the process of these disorders. CONCLUSION: Our case-control study in the Iranian population suggested a possible association between the mentioned single-nucleotide polymorphisms and CAD in T2D patients. However, further replication studies and comprehensive meta-analyses are required.

Association of -77T>C and Arg194trp polymorphisms of XRCC1 with risk of coronary artery diseases in Iranian population.

OBJECTIVES: Coronary artery disease (CAD) is the leading cause of death in both male and female worldwide. The main cause of CAD is the atherosclerosis of coronary arteries, which is, mostly caused by genetic alteration. 50% of such cases occur in mitotic cells where single-strand breaks occur spontaneously or due to ionizing radiation. X-ray repair cross-complementing protein 1 (XRCC1) as a key element, participate in the base excision repair (BER) and Single-strand Break Repair (SSBR) pathways. It has been suggested that XRCC1 functions as a scaffold protein able to coordinate and facilitate the various steps of DNA repair pathways. Two Single Nucleotide Polymorphisms (SNPs) (Arg194Trp and -77T>C) were reported to affect the function and expression of XRCC1, respectively. MATERIALS AND METHODS: A case-control study was performed to investigate the relation between these polymorphisms and the CAD development. A population of 406 individuals was screened for SNPs by Restriction Fragment Length Polymorphisms (RFLP) method. RESULTS: XRCC1 Arg194Trp polymorphism was associated with increased risk of CAD in examined population under a dominant model (Odds-ratio=2.604, P-value=0.001). Also the SNP of -77T>C revealed a protective role in the population under a dominant model (Odds-ratio=0.618, P-value=0.032). CONCLUSION: Our findings demonstrated a contributory role of these two SNPs in CAD. Furthermore, our results support the role of DNA damages and the malfunctions of DNA repair system in cardiovascular disease development in Iranian patients.

Cholesteryl ester transfer protein gene polymorphism (I405V) and premature coronary artery disease in an Iranian population.

The effect of human cholesteryl ester transfer protein (CETP) expression on atherogenesis is still under debate. The rs5882 (I405V) polymorphism affect CETP function. We aimed to examine the relationship between the rs5882 polymorphism and the risk of angiographically determined coronary artery disease (CAD). To define premature CAD (PCAD), an age cutoff of 55 years for women and 45 years for men was used. An age- and sex-matched case-control study was conducted in 560 patients with newly diagnosed angiographically documented PCAD (≥50% luminal stenosis of any coronary vessel) and an equal number of control patients with normal coronary arteries (no luminal stenosis at coronary arteries). The severity of CAD was determined by vessel score and Gensini score. A real-time polymerase chain reaction (PCR) and high resolution melting analysis were used to distinguish between genotypes. The I405V genotype distributions were not statistically different in CAD and non-CAD groups in univariate and multivariable-adjusted logistic regression analyzes. The median and inter-quartile range for Gensini score was not significantly different among the AA (43, 24 to 73), AG (40, 20 to 66), and GG (45, 25 to 72) genotypes (p = 0.097). Furthermore, the distribution of vessel score did not statistically differ between these genotypes (p = 0.691). Our results suggest that there is no significant association between CETP I405V polymorphism and the risk of PCAD presence and severity. Larger prospective studies are needed to investigate such associations in different populations.