جستجوی مقالات مرتبط با کلیدواژه « genetic polymorphism » در نشریات گروه « پزشکی »

Endometriosis is a chronic, gynecological disorder, and the disease's pathogenesis is still debatable. Genes related to apoptosis have been revealed to be deregulated in endometriosis.

This study investigates the relationship between polymorphic variants of Bax -248G>A and Bcl-2 -938C>A promoter regions with endometriosis risk in an Iranian population.

In this case-control study, the polymorphisms of Bax -248G>A and Bcl-2 -938C>A promoter regions were analyzed in 127 Iranian cases and 125 controls who were referred to Ali-ibn-Abi Taleb Educational hospital, Zahedan, Iran between May 2022 and February 2023. The genotypic analysis was performed for all the subjects using the polymerase chain reaction-restriction fragment length polymorphism method.

The frequencies of mutant allele A carriers and the A allele of Bax -248G>A polymorphism showed about 2-fold significant increase of endometriosis risk (p = 0.04; p = 0.01, respectively). The frequencies of the mutant genotype AA and A allele carriers of Bcl-2 -938C>A polymorphism were approximately 4 and 2.5-fold higher in endometriosis compared to the control women, which were highly significant (p > 0.001). Moreover, the allele A frequency of Bcl-2 -938C>A was associated with a 2-fold higher risk of endometriosis (p > 0.001). Furthermore, the combination effects of these 2 single nucleotide polymorphisms showed that women with Bax -248G>A GG and Bcl-2 -938C>A AA variant alleles were associated with about 5 times higher risk of endometriosis (p > 0.001). Notably, a significant difference was observed in mutant allele distribution between minimal/mild (stage I and II) and moderate/severe (stage III and IV) women with endometriosis disease.

The results of our study provide evidence that Bcl-2 -938C>A and Bax -248G>A single nucleotide polymorphisms might be associated with the risk of endometriosis.

Host genetic changes like single nucleotide polymorphisms (SNPs) are one of the main fac- tors influencing susceptibility to viral infectious diseases. This study aimed to investigate the association between the host SNP of Toll-Like Receptor3 (TLR3) and Toll-Like Receptor7 (TLR7) genes involved in the immune system and susceptibil- ity to COVID-19 in a sample of the Iranian population.

This retrospective case-control study evaluated 244 hospitalized COVID-19 patients as the case group and 156 suspected COVID-19 patients with mild signs as the control group. The genomic DNA of patients was gen- otyped for TLR7 (rs179008 and rs179009) and TLR3 (rs3775291 and rs3775296) SNPs using the polymerase chain reac- tion-restriction fragment length polymorphism (PCR-RFLP) method.

A significant association between rs179008 SNP in the TLR7 gene and the susceptibility of COVID-19 was found between case and control groups. The AT genotype (Heterozygous) of TLR7 rs179008 A>T polymorphism showed a sig- nificant association with a 2.261-fold increased odds of COVID-19 (P=0.003; adjusted OR: 2.261; 99% CI: 1.117-4.575). In addition, a significant association between TC genotype of TLR7 rs179009 T>C polymorphism and increased odds of COVID-19 (P< 0.0001; adjusted OR: 6.818; 99% CI: 3.149-14.134) were determined. The polymorphism frequency of TLR3 rs3775291 and rs3775296 genotypes were not significantly different between the case and control groups (P> 0.004167).

SNPs in TLR7 rs179008 and rs179009 genotypes are considered host genetic factors that could be influenced individual susceptibility to COVID-19. The SNPs in TLR3 (rs3775296 and rs3775291) showed no significant association with COVID-19 in Iranian population.

 Early immune responses to COVID-19 can help eliminate the virus; therefore, strategies to improve the immune system have become important in disease prevention. Vitamin D plays a crucial role in the immune response to SARS-CoV-2 by increasing the expression of the vitamin D receptor.

 This study investigated the impact of vitamin D deficiency, Fok 1, and Taq 1 Vitamin D Receptor (VDR) gene polymorphisms and comorbidities on the susceptibility to COVID-19.

 Fok1 and Taq1 polymorphisms were analyzed using the RT-PCR method, and vitamin D levels were measured using the chemiluminescence method. A total of 200 patients, 100 with COVID-19 and 100 without, provided blood samples for analysis.

 The COVID-19 positive group had a significantly lower mean vitamin D level of 16.2 ± 11.3 ng/mL compared to the COVID-19 negative control group, 26.7 ± 15.9 ng/mL (P < 0.001). Individuals with a vitamin D level below 18.4 ng/mL had a 2.448 times higher risk of COVID-19 positivity (P < 0.001). There was no significant difference in the Fok1 and Taq1 gene polymorphisms between the two groups. (P = 0.548 and P = 0.098). The COVID-19 positive group had a significantly higher number of comorbid diseases with 40 (40%) compared to the negative group with 10 (10%) participants (P < 0.001).

 Levels of vitamin D above the cut-off value of 18.4 ng/mL were found to protect against COVID-19, while the presence of comorbid diseases was identified as a risk factor. However, no association was observed between the Fok1 and Taq1 polymorphisms and susceptibility to COVID-19.

Genetic polymorphisms are predictors of the immune response and susceptibility to certain infectious diseases, including pulmonary tuberculosis (TB). We evaluated the association of monocyte chemoattractant protein-1 (MCP1) (-2581 A/G) and interferon-gamma (IFNγ) (+874 T/A) polymorphisms with susceptibility to pulmonary TB in an Iranian population.

A total of 124 patients with pulmonary tuberculosis and 244 healthy subjects (121 related normal controls and 123 unrelated subjects) were included. The MCP1 polymorphic region (-2518 A/G) was genotyped by PCR-RFLP, while ARMS-PCR was used to amplify and detect IFNγ (+874 T/A). SNPStats and SPSS v. 20 were used for the statistical analysis of the data.

The comparison of MCP1 (-2518 A/G) alleles and genotypes in TB patients and healthy subjects showed no significant association in all the constructed heredity models. No association was observed between TB patients and normal subjects in all the constructed inheritance models for IFNγ (+874 T/A) alleles and genotypes.

Due to the lack of association between MCP1 (-2518 A/G) and IFNγ (874 T/A) polymorphisms and susceptibility to PT in our study and the conflicting results of some previous studies, further clinical and molecular research is needed to clarify the role of the studied polymorphisms in the pathogenesis of tuberculosis.

Rotator Cuff Tear (RCT) is a multifactorial disease, but an important one is the increased collagen degradation that would lead to a higher chance of tear. MMP-8 is a protein that degrades type I collagen, and it is known that MMP-8 has a polymorphism in which a T allele in the gene promoter region increases its transcription activity. This study aims to investigate the association between MMP -8 polymorphism g.-799 C>T (rs11225394) and RCT. To do that, we collected DNA samples from buccal epithelial cells of 128 patients (separated into RCT group and control group in a proportion 1:1) and genotyped the DNA using PCR. The statistical analyses were done using the ARLEQUIN Version 2.0, and the data normality was tested with the Shapiro-Wilk test. The results showed a significantly higher frequency of T/T genotype in the test group (29% in the control group and 39% in the test group, p=0.0417), and that would represent a risk factor for increased collagen degradation. The MMP-8 g.-799 C>T (rs11225394) SNP was associated with RCT. With the description of a new risk factor, future research can be done to analyze how to prevent RCT or develop new treatment strategies since the disease's failure index is currently high. Level of evidence: II

Migraine is a multifactorial neurological disorder characterized by frequent moderate to severe intensity headaches. The genetic variations in synaptic and post-receptor signalling proteins have direct effect on the process of serotonergic neurotransmission. We aimed to investigate the genetic association of serotonin transporter (SERT) 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) polymorphism and migraine risk in South-Indian population. A total of 304 subjects with migraine including with aura (MA) and without aura (MO) and 308 controls were included in the present study. The single nucleotide polymorphism (SNP) was detected using polymerase chain reaction (PCR) and confirmed by deoxyribonucleic acid (DNA) sequencing. The genotyping analysis revealed insignificant relationship with migraine subjects when compared with controls (P > 0.05). The minor ‘S’ allele showed no association with odds ratio (OR) = 1.23 [95% confidence interval (CI): 0.90-1.66], heterozygote with OR = 1.18 (95% CI: 0.82-1.69), and homozygote with OR = 1.51 (95% CI: 0.52-4.35). Further clinical studies are required to validate the results of SERT 5-HTTLPR promoter polymorphism in diverse ethnic descents especially in Asian populations.

Chronic periodontitis (CP) is characterized by an immune response, leading to the destruction of periodontal supporting tissue. The effect of inflammatory and genetic factors on periodontitis has been evaluated previously. The interleukin (IL‑17) as an inflammation regulator seems to play a critical role in periodontitis pathogenesis. Here, in the current study, we aimed to investigate the association of ‑197 G > A (rs2275913) IL‑17 gene promoter polymorphism with generalized severe CP in an Iranian population.

In this case–control study, a total of 54 patients with periodontitis and 118 normals were enrolled. The polymerase chain reaction‑restriction fragment length polymorphism technique was applied to detect IL‑17 promoter rs2275913 genotypes in association with the susceptibility to severe CP. Chi‑square test or Fisher’s exact test was employed to compare genotype frequencies between groups. P < 0.05 were considered statistically significant.

The distribution of genotypes and alleles was in Hardy–Weinberg equilibrium. Although no significant association was observed between the risk of periodontitis and genotype frequencies under any of the inheritance models, the GG genotype was higher in healthy controls, while the AG genotype was more frequently observed in patients under the codominant model ([odd ratio [OR] = 2.14, 95% confidence interval (CI) (1.01–4.53), P = 0.13]). The frequency of AG‑AA genotype was higher in patients under dominant inheritance model ([OR = 1.92, 95% CI (0.94–3.93), P = 0.068]), while GG‑AA and AG genotypes were higher in healthy controls under over dominant model (OR = 0.1.95, 95% CI [0.98‑3.86], P = 0.055).

The results of this study showed that the presence of allele A and AG genotypes could be considered possible factors in increasing the risk of developing CP, although the differences of allele and genotype frequencies were remarkable but not statistically significant between the two groups.

Genetics has been found to have a prominent role in autism and therefore pharmacogenetics may guide us to a better management of this disorder. Given the importance of Renin-Angiotensin System (RAS) in the function of the brain and its possible association with autism, genetic variations of RAS may influence response to autism treatment. In this study, 83 autistic children were enrolled (3 to 12 years of age). Degree of autism was confirmed by the DSM-V criteria and response to treatment was measured according to Aberrant Behavior Checklist (ABC) scale at baseline, at 4 and 12 weeks of risperidone therapy. Polymorphisms (ACE I/D, rs4343 and rs4291) were determined by PCR-RFLP. Our results indicate the positive role of long term therapy in autism (12 weeks vs 4 weeks). The highest response rate in ACE ID gene was in the DD genetic variant at both 4 and 12 weeks of treatment. For the ACE A2350G gene, all genetic variants did not respond well to treatment at 4 weeks, however at 12 weeks, positive response was dominant in the AG genetic variant. Highest response rate in the ACE A240T gene belonged to the AT variant at both 4 and 12 weeks of treatment. However, our results indicate no significant association between ACE gene polymorphisms and response to risperidone therapy in autistic children based on ABC scaling. In conclusion, this study does not support the hypothesis of involvement of RAS genetics in response to risperidone in autistic children.

This study aims to evaluate the catalytic activities of 31 CYP2C19 alleles and their effects on the metabolism of tapentadol in vitro. 

Insect microsomes expressing the CYP2C19 alleles were incubated with 50–1250 μM tapentadol for 40 min at 37 °C and terminated by cooling to -80 °C, immediately. Tapentadol and N-desmethyl tapentadol were analyzed by a UPLC-MS/MS system. The kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of N-desmethyl tapentadol were determined. 

As a result, the intrinsic clearance (Vmax/Km) values of most variants were significantly altered, while CYP2C19.3 and 35FS had no detectable enzyme activity. Only one variant, N277K, showed no significant difference from CYP2C19.1B. Two variants CYP2C19.29 and L16F displayed markedly increased intrinsic clearance values of 302.22% and 199.97%, respectively; whereas 24 variants exhibited significantly decreased relative clearance ranging from 0.32% to 79.15% of CYP2C19.1B. Especially, CYP2C19.2G, 2H, R124Q, and R261W exhibited a drastic decrease in clearance (>80%) compared with wild-type CYP2C19.1B. 

As the first study of all aforementioned alleles for tapentadol metabolism, the comprehensive data in vitro may provide novel insights into the allele-specific and substrate-specific activity of CYP2C19.

Cardiovascular disease is one of the most common causes of morbidity and mortality worldwide. The Proline and Serine Rich Coiled-Coil 1 gene in 1p13.3 locus has been reported to be associated with low density lipoprotein cholesterol (LDL-C) and coronary artery disease (CAD). The objective of this study was to investigate the association between the rs599839 polymorphism of the Proline and Serine Rich Coiled-Coil 1 (PSRC1) gene with CVD outcomes in a population sample recruited as part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort.

Five hundred and nine individuals who had an average follow-up period of 10 years were enrolled as part of the MASHAD cohort. DNA was extracted and genotyped using the TaqMan-real-time-PCR based method.

The study found individuals with GA/GG genotypes were at a higher risk of CVDs (OR= 4.7; 95% CI, 2.5-8.7; p< 0.001) in comparison to those with AA genotype; however, the result was not significant for GG genotype data.

The results suggest that the GA/GG genotypes of the PSRC1gene locus were at increased risk of CVD in a representative population-based cohort, demonstrating further functional analysis to discover the value of emerging marker as a risk stratification biomarker to recognize high risk cases.

Chemokines are proinflammatory cytokines that play key roles in development of cardiovascular diseases (CVD). Chemokine-induced recruitment of peripheral leucocytes to tissues is a crucial step in the CVD progression. CC chemokines ligand 5, 2 (CCL5 and CCL2), have been characterized as emerging inflammatory biomarkers of atherosclerotic CVD. The aim of this study was to find out whether genetic polymorphisms of CCL5 -403 G>A (rs2107538) and CCL2 –927 G>C, (rs3760396) were associated with the risk of CVD.

In this case-control study, 500 Iranian individuals including 250 CVD patients and 250 healthy subjects as the control group participated in 2017. Genotyping of CCL5 -403 G>A and CCL2 –927 G>C polymorphisms were executed using Tetra-ARMS PCR method.

At genotypic level both CCL5 -403 G>A and CCL2 –927 G>C polymorphisms were not associated with the risk of CVD (P>0.05), even after adjustment by age, sex, race, and history of hypertension, DM and smoking. However, the CCL2 –927 C allele was associated with an increased risk of CVD (OR=1.42, P=0.050) with a higher prevalence in CVD patient than in controls (17% vs. 12%). Moreover, the haplotype analysis revealed that CCL5/CCL2 haplotype (G/C) was a risk factor for CVD (OR=2.13, P=0.001), and that carriers of this haplotype were at 2.13-fold higher risk of CVD than subjects with G/G haplotype.

CCL2 –927 C variant and CCL5/CCL2 haplotype (G/C) were associated with susceptibility to CVD, and were risk factors for CVD in our population but more studies with large sample size are recommended.

During pregnancy, the embryo implantation stage is a highly dynamic and molecularly controlled phenomenon. Several genes are involved in the implantation process, among which the leukemia inhibitory factor (LIF) is a marker of implantation. LIF is a multi-functional cytokine located on chromosome 22. The expression of this gene is increased in the middle of the secretion phase from the sexual cycle, and any defect in its expression will cause the implantation failure. LIF receptor or LIFR gene, as the LIF receptor, consists of two membrane proteins called LIFR and GP130. LIFR acts as a signal receptor for LIF in a low-affinity level. In this study, we focused on the screening of polymorphisms in the promoter region of the LIF and LIFR genes in the infertile women using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method. In this study, blood samples were collected from 100 women with primary and secondary infertility and 50 healthy women as a control group. Extraction of DNA was done by the phenol-chloroform method, and in the next step, using specific primers for upstream regions of the LIF and LIFR genes, target sequences were amplified and analyzed by the SSCP method. Finally, PCR products with different configurations were selected for sequencing analysis. The results showed two polymorphisms in the upstream region of LIF and LIFR genes of two women, but there were no genetic changes in the control group. The present study was the first in this field, and the results indicated the importance of examining such genes in infertility with an unknown cause.

The requirement of varying doses of warfarin for different individuals can be explained by environmental and genetic factors. We evaluated the frequency of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) variants together with patientdemographic characteristics and investigated their association with warfarin dose requirement with the objective to suggest a warfarin dosing algorithm. In this study, 185 patients with heart valve replacement from West Azerbaijan, Iran were genotyped for VKORC1 (-1639 G>A) and CYP2C9 (*2 and *3 alleles) by PCR-RFLP. Multiple linear regression was performed to create a new warfarin dosing algorithm. The frequency of variants in studied subjects was 12% for CYP2C9 *2, 25.8% for CYP2C9 *3, and 60% for -1639A. The patients who carried the A allele at position -1639 VKORC1 and the variants CYP2C9 *2 and *3 required a significantly lower daily mean warfarin dosage (P = 0.001). Statistical analysis also indicated a significant relationship between the daily maintenance dose of warfarin with age and blood pressure among the studied patients’ cohort (P < 0.001). This study showed that in the heart valve replacement patients considering VKORC1 and CYP2C9 polymorphisms beside demographic characteristics such as age will be helpful in pre-treatment dosing of warfarin which in turn reduces the complications associated with inappropriate warfarin dosing.

The current study aimed to investigate the relationship of genetic polymorphism and plasma methotrexate (MTX) levels, toxicity experience and event free survival (EFS) in pediatric acute lymphoblastic leukemia (ALL).

The study included 74 ALL patients. Polymerase chain reaction and genotyping of methylene tetrahydrofolate reductase (MTHFR) rs1801133, MTHFR rs1801131, ATP-binding cassette superfamily B1 (ABCB1) rs1045642, ATP-binding cassette superfamily G2 (ABCG2) rs2231142 and solute carrier 19A1 (SLC19A1) rs1051266 genetic variations were performed. The plasma MTX levels were investigated at 48 hr after the first dose of MTX infusion.

MTHFR rs1801133 TT genotype, ABCBa1 rs1045642 CT genotype and ABCG2 rs2231142 CA genotype revealed a statistically significant association with the MTX plasma levels (P<0.01, P<0.05, P<0.05, respectively). The MTHFR rs1801133 TT genotype had a statistically significant association with hematopoietic toxicity (P<0.01) and interventions (P<0.05). The MTHFR rs1801131 AC genotype was related to the decreased hepatic toxicity (P<0.05). The SLC19A1 rs 1051266 GA genotype was related to the increased hepatic toxicity (P<0.05). Only the ABCB1 rs1045642 CT and TT genotypes had a statistically significant correlation with EFS (P<0.05, P<0.05, respectively).   

Our findings showed that genetic polymorphism could be associated with plasma MTX levels, toxicity experienced and EFS in Iranian pediatric ALL.

Tramadol overdose is inappropriately prevalent in Iran and is one of the most common causes of hospital admissions in recent years. Tramadol is both a codeine family and a weak opioid receptor agonist (AG) that is used at regular doses as an analgesic and may lead to seizures. The aim of this study was to investigate the relationship between physiological effects of high dose tramadol administration and cytochrome c enzyme gene polymorphism. CYP2D6) p450) in patients with tramadol intoxication referring to the poisoning ward of Razi Hospital, Ghaemshahr city,Mazandaran province was surveyed. This cross-sectional study was performed on 121 patients admitted for poisoning ward of Tramadol only in 2016. Also, these patients do not have any previous underlying diseases such as cardiac and renal complications, etc. 60 of the patients had seizure due to tramadol. At first, demographic characteristics of patients and factors evaluated were extracted in a questionnaire and ml of each patient. 5th was taken blood. After preparing the samples, RFLP - PCR was used to evaluate the CYP2D6 gene polymorphism (rs1065852). The mean age of patients was 25 years. 78% of them were smokers. Statistical methods were considered as p