Polymorphism In Iranian Patients Research Articles

VEGF gene polymorphisms in Iranian patients with intracranial glioblastoma.

Glioblastoma is one of the most common malignant brain tumors in adults with poor prognosis. Neovascularization is one of the characteristics of these tumors, which is associated with overexpression of vascular endothelial growth factor (VEGF). Accordingly, single nucleotide polymorphisms of this gene could play an important role in structural and functional alterations leading to overexpression of this gene in GBM. A total number of 49 patients with GBM and 50 healthy controls were included in the current study. The Genomic DNA was extracted from brain tumor/tissue samples, and after purification assessment, the alleles, and genotypes of rs3025039 and rs2010963 polymorphisms of the VEGF gene were investigated using T-ARMS-PCR. The "T" allele of rs3025039 was 2.79 times more frequent in GBM patients compared to controls (P=0.01). Moreover, the "CT" genotype was 2.83 times more common among patients (P=0.015), while the "CC" was more frequent in controls (P=0.009). The mean overall survival was significantly different between three genotypes of rs3025039, with the longest survival time in "CT" genotype (15.10±5.21, P=0.041). Besides, rs2010963, was significantly associated with GBM occurrence, with the "G" allele being 1.96 times more frequent in patients (P=0.01), as well as the "GG" genotype, which was 7.87 times more common in patients (P<0.001). Polymorphisms of VEGF could potentially play a role in pathogenesis of GBM, as the allele and genotype distributions of rs3025039 and rs2010963 SNPs were significantly associated with GBM occurrence.

MGMT Gene rs1625649 Polymorphism in Iranian Patients with Brain Glioblastoma: A Case Control Study.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with poor prognosis and high potential of dispersion to other brain tissues in adult. Effective and modern choices of treatment including chemotherapy with alkylating agents marginally extend survival of GBM. However, alkylating agents can lead to highly harmful mismatch during DNA replication causing apoptosis and cell death. Accordingly, O6-Methylguanine-DNA methyltransferase (MGMT) removes alkyl adducts, thereby causing resistance to alkylating drugs. Single-Nucleotide Polymorphisms (SNPs) in MGMT promoter region may play a role in the regulation of MGMT expression and prediction of glioma development risk. In order to evaluate the clinical significance of rs1625649 SNP in the MGMT promoter region of glioblastoma, genomic DNA from a series of 54 patients with GBM and 50 healthy individuals in Iranian population were collected for tetra ARMS PCR amplification. None of the "A" or "C" alleles were associated with tumor occurrence, the "AA" genotype was more frequent in healthy subjects, and the "AC" genotype was 4.6 times more common in patients with GBM. The longest survival time was observed in the "CC" genotype; however, this difference was not statistically significant. On the other hand, homozygous rs1625649 (AA genotype) was significantly associated with a better survival than the cases with heterozygous rs1625649 (CA genotype) or wild type rs1625649 (CC genotype), predicting better response to temozolomide-based chemotherapy.

Genotyping of ARNTL and CLOCK Circadian Rhythm Gene Polymorphisms in Iranian Patients with Multiple Sclerosis

Background: Multiple sclerosis (MS) is a central nervous system disease accompanied by variable symptoms such as optic neuritis, fatigue, spasticity, neuro-urological dysfunction, paresthesia, and headache. The frequency of MS was reported differently in geographical latitude, which may be in relation to genetic changes in circadian rhythm regulator genes, including aryl hydrocarbon receptor nuclear translocator-like (ARNTL) and circadian locomotor output cycles kaput (CLOCK). Objectives: This study aimed at genotyping rs3789327 in the ARNTL and rs6811520 in the CLOCK genes and their association with MS in the Iranian population. Methods: Totally, 100 patients with relapsing-remitting multiple sclerosis (RRMS) and 100 healthy controls were recruited. DNA extracted from the whole blood of all patients was genotyped by high-resolution melting (HRM) real-time PCR method for the rs3789327 and rs6811520 within the ARNTL and CLOCK genes, respectively, then the HRM results were confirmed by Sanger sequencing method. Results: Our results showed a statistically significant difference in genotype distributions in the CLOCK gene (rs6811520, P = 0.023) in MS and healthy controls, but in the ARNTL gene, there was no significant change in rs3789327 genotypic distribution between MS patients and healthy individuals (P = 0.2). The TC genotype of the rs6811520 was associated with a higher risk for MS [P = 0.006, OR = 4.164, 95% confidence intervals (CI) 1.43 - 12.09]. Conclusions: The present results suggested that genetic variations in the CLOCK gene are a risk factor for MS.

DNA sequencing validation by PCR-RFLP for evaluating butyrophilin-like 2 rs2076530 polymorphism in Iranian patients with sarcoidosis.

Background:Sarcoidosis is a multifactorial immune disorder with an uncertain origin. A single nucleotide polymorphism (G→A, rs2076530) in the butyrophilin-like 2 (BTNL2) gene results in the formation of truncating protein. This study aimed to genotype the predisposition of the BTNL2 rs2076530 polymorphism in Iranian patients with sarcoidosis using the RFLP technique.Materials and Methods:In this study, 80 patients with sarcoidosis and 80 healthy individuals were included. The rs2076530 polymorphism of the BTNL2 gene was genotyped using the PCR-RFLP method by AvrII restriction enzyme and confirmed by DNA sequencing (Capillary electrophoresis 3130, ABI).Results:There was a statistically significant difference between proportions of patients with AA (47,5%) and controls (27.5%) (OR=2.38, 95%CI:1.23-4.61, P=0.009). In addition, a significant difference was observed in the frequency of the A allele (62.5%) in sarcoidosis (OR=2.14, 95%CI:1.37-3.35, P=0.001). A Bonferroni correction with P<0.0038 indicates a statistical difference for genotype AA (P=0.009). In an effective model, binary logistic regression analysis indicates a statistical association between AA genotype and sarcoidosis (P=0.018 with 60% prediction). Based on the gene analysis study using DNA sequencing, all of the mentioned mutations were seen via RFLP.Conclusion:According to our findings, the BTNL2 rs2076530 A allele in the Iranian population is associated with susceptibility to sarcoidosis. This designed PCR-RFLP method for detecting SNPs is effective as DNA sequencing.

The relationship between IL23R 1142G / A (Arg381Gln) and GM-CSF 3928 C / T (Ile117Thr) gene polymorphism in Iranian patients with tuberculosis disease

The DNA polymorphisms found in clinical strains of Mycobacterium tuberculosis drive altered physiology, virulence, and pathogenesis in them. This study aimed to investigate the association between IL23R 1142 G/A (Arg381Gln) and GM-CSF 3928 C/T (Ile117Thr) gene polymorphisms with the incidence rate of tuberculosis in the population of Sistan. This study was based on the descriptive and applied type. All patients with active pulmonary tuberculosis were referred to the tuberculosis center of Zabol city for one year, with an equal number of healthy people adapted to the patients examined in terms of age. After data collecting to compare the frequency of polymorphisms, the chi-square test and OR index were used using SPSS software version 16. We have found that the IL23R reduced-function allele 1142A and genotypes CC and TC were overrepresented, especially in the Pad subgroup compared with the control group (44% versus 42%, 21% versus 22%, and 44% versus 39%, respectively. Increased risks of TB with minimal/moderate lung involvement, respectively. Our results demonstrate that the reduced-function polymorphism 1142G ¡ A encoded by IL23R influences the outcome of disease severity of active pulmonary TB in ZABOL patients. The genotypic and allelic frequency of IL23R 1142 G/A, and GM-CSF 3928 C/T (Ile117Thr) polymorphism in patients with tuberculosis was significantly different from the control group and this polymorphism was associated with the incidence of tuberculosis in the population of Sistan.

CYP3A4⁎22 gene polymorphism and risk of ischemic stroke in south Iran population: A case control study

Cytochrome P450 3A4 (CYP3A4), the main drug-metabolizing enzyme in the liver, has a functional SNP in intron six named CYP3A4⁎22. Given the CYP3A4⁎22 polymorphism effect on the reduced CYP3A4 mRNA/protein expression, this study aimed to evaluate the prevalence of CYP3A4⁎22 polymorphism in Iranian patients with stroke compared to the control group. A total of 175 patients with stroke and 236 control age-sex matched ones have been examined for CYP3A4⁎22 polymorphism by Tetra ARMS-PCR methods. The results were confirmed by the PCR-RFLP technique and the sequencing of DNA. This study is the first report of CYP3A4⁎22 polymorphism from Iran. The frequency of the CYP3A4⁎22 wild-type (GG genotype) and heterozygous genotypes (GA genotype) was 93.1% and 6.9% in patients, and 92.8% and 7.2% in the controls, respectively. None of the participants was the recessive model for this polymorphism. There were no statistical differences between the patient and control groups (p > 0.05). Also, the GA genotype was not associated with increased risk of stroke compared with the GG genotype (OR = 0.95, 95% CI: 0.44–2.04, P = 0.892). Since CYP3A4⁎22 polymorphism may result in reduced CYP3A4 activity in vivo, due to the large number of drugs that are CYP3A4 substrates, individuals with this polymorphism may experience unusual drug effects. To clarify these impacts, further investigations are, therefore, needed to be done.

Evaluation of glutathione S-transferase polymorphism in Iranian patients with type 2 diabetic microangiopathy

BackgroundOverproduction of reactive oxygen species as a result of hyperglycemia in diabetes mellitus leads to microvascular complications. Glutathione S-transferases play important detoxifying roles with antioxidant potentials. This study aimed to assess whether the glutathione S-transferase M1 and T1 genotypes were associated with type 2 diabetes mellitus microangiopathic complications in the Iranian population.ResultsIn this case-control study, the frequencies of null GSTM1 and GSTT1 genotypes were 4/72 (5.56%) and 12/72 (16.67%) respectively, in uncomplicated DM group. The frequencies of null GSTM1 and GSTT1 genotype in complicated DM group were 16/134 (11.94%) and 37/134 (27.61%), respectively. The proportion of GSTM1 null genotypes was higher in diabetic nephropathy compared to non-nephropathy (19.3% vs. 6.04 %, P = 0.006). At GSTT1 locus, patients with diabetic peripheral neuropathy had a higher frequency of deletion compared to those of without neuropathy (30.39% vs. 23.49%) (P = 0.02).ConclusionSelective polymorphisms encoding GSTM1 and GSTT1genes may prove useful as genetic markers to recognize individuals with an increased trend in developing diabetic nephropathy and neuropathy, respectively. This will help better identify individuals at higher risk toward microvascular complications of type 2 diabetes due to genetic susceptibility.

Aldose reductase (AC)n gene polymorphism in Iranian patients with type 2 diabetic microangiopathy; a case-control study.

(AC)n promoter region of the aldose reductase (ALR) genes polymorphism has been associated with diabetic microvascular complications (MVCs). The aim of this study was to find the relationship between dinucleotide repeat (AC)n polymorphisms of the ALR gene and the occurrence of MVCs, such as diabetic retinopathy, neuropathy, and nephropathy in Iranian type 2 diabetic (T2D) patients. This prospective case-control study was performed on T2D patients who were categorized into two groups based on the presence or absence of diabetic microangiopathy. All patients were provided informed consent. After extracting genomic DNA, the (AC)n of the ALR gene was determined using Polymerase chain reaction (PCR). Thirteen alleles of the (AC)n gene polymorphism were detected including Z + 16, Z + 14, Z + 8, Z + 6, Z + 4, Z + 2, Z, Z-2, Z-4, Z-6, Z-8, Z-10, and Z-12. The frequency of the Z-4 allele was significantly higher in patients with retinopathy, nephropathy, and autonomic neuropathy compared with those with long-term uncomplicated diabetes (P < 0.001, P < 0.001, P = 0.031, respectively). After controlling for baseline risk factors, we found that the carrier of the Z-4 allele of ALR (AC)n polymorphism had a higher risk of diabetic retinopathy and diabetic nephropathy (P < 0.001). The homozygosity for the Z-4 allele was found to be associated with diabetic microangiopathy. Our results showed that ALR (AC)n gene polymorphism in Iranian patients with type 2 diabetes independently, predispose retinal, renal and neural microvascular to diabetic complications.

Evaluation of TP53 Codon 72, P21 Codon 31, and MDM2 SNP309 Polymorphisms in Iranian Patients with Acute Lymphocytic Leukemia.

The tumor suppressing protein p53 and its downstream effector p21 play important roles in cell cycle regulation. Deficiency or deactivation of these proteins as a result of gene alterations has been indicated in several cancers. Such genetic variations could be considered as susceptibility indicators in acute lymphocytic leukemia (ALL). Therefore, we investigated the associations between ALL risk and TP53 codon 72, p21 codon 31, and MDM2 SNP309 polymorphisms in an Iranian population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the MDM2 T309G (rs2279744), TP53 codon Arg72Pro (rs1042522), and p21 Ser31Arg (rs1801270) single nucleotide polymorphisms (SNPs). This study was performed in 115 ALL patients and 115 healthy controls in Khuzestan province in southwest Iran. In the control group and ALL patients, p21 Ser/Arg, and MDM2 TG and GG genotypes were associated with significant 1.81-fold (95% confidence interval CI= 1.008-3.267; P < 0.05), 11.07-fold (95% CI= 5.10-24.05; P < 0.0001), and 19.41-fold (95% CI= 8.56-43.99; P < 0.0001) increased risks for ALL, respectively. The TP53 72 Arg allele was significantly more prevalent in ALL patients (56.96%) than in control subjects (47.39%), and was significantly associated with ALL (OR= 1.47; 95% CI = 1.017-2.121, P < 0.05). The MDM2T309G and the p21 Ser31Arg SNPs indicate a significantly increased risk for developing ALL in Khuzestan province.

Interleukin-23 receptor gene polymorphisms in Iranian patients with juvenile systemic lupus erythematosus

Introduction and objectivesConsidering the possible roles of interleukin-23 receptor (IL-23R) gene in the pathogenesis of juvenile systemic lupus erythematosus (JSLE), the objective of this study was to elucidate whether polymorphisms of the IL23R are associated with susceptibility to JSLE in an Iranian population. Materials and methodsA case-control study on 62 patients with JSLE and 78 healthy controls was performed to investigate the associations of four single nucleotide polymorphisms (SNPs) in IL-23R gene, namely, rs7517847, rs10489629, rs11209026, and rs1343151, with susceptibility to JSLE, using real-time polymerase chain reaction Taqman genotyping technique. ResultsAnalysis of allele and genotype frequency of four selected SNPs revealed statistically significant positive association between homozygous variant of rs7517847 (TT) (P, 0.02) and T allele at the same position (P, 0.01) with JSLE vulnerability. There was no significant association between other evaluated SNPs and JSLE susceptibility. ConclusionThese findings suggest that particular IL-23R gene variants could affect individual susceptibility to JSLE.

Association of Matrix Metalloproteinase-1 -1607 1G/2G and C-Reactive Protein -717 C/T Gene Polymorphisms in Iranian Patients with Chronic Periodontitis: A Clinical Trial

Background: An imbalance in the expression of matrix metalloproteinases (MMPs) and tissue inhibitor metalloproteinases initiate the destructive process in chronic periodontitis (CP). C-reactive protein (CRP) is a systemic inflammatory mediator that reflects an acute immune response.Objectives: The purpose of this investigation was to analyze the association between the MMP-1 -16071G/2G (rs1799750) and CRP 717 A/G (rs2794521) gene polymorphisms and chronic periodontitis in Iran.Methods: This analytical case-control study was performed among 141 participants including 63 CP cases and 78 matched healthy individuals. Five milliliters of peripheral blood was collected for DNA isolation. Restriction fragment length polymorphism- polymerase chain reaction (RFLP-PCR) was performed for single-nucleotide polymorphism (SNP) analysis. The frequencies were analyzed by chi-squared test (95% CI, P < 0.05). In addition, genetic data were assessed by the Hardy-Weinberg principle, linkage disequilibrium, and haplotype analysis.Results: Our findings presented no significant relationship between genotype/alleles of MMP-1 -16071G/2G (rs1799750) (0.73: 0.27-1.95, P = 0.48) or CRP 717 A/G (rs2794521) (0.384: 0.104 -1.414, P = 0.303) and the presence of CP (P = 0.47 and P = 0.30, respectively). The analysis of genetic distribution among various severities of CP and controls revealed no significant association between various severities of CP and MMP-1 -16071G/2G (rs1799750) (P = 0.52) and CRP 717 A/G (rs2794521) (P = 0.67).Conclusions: Our results suggest no association between the occurrence or severity of chronic periodontitis and MMP-1-16071G/2G (rs1799750) and CRP 717 A/G (rs2794521) polymorphisms. Further studies with larger sample sizes may provide a more generalizable evidence-based overview of the relationship between these gene polymorphisms and periodontitis.

Association of vitamin D binding protein and vitamin D receptor gene polymorphisms in Iranian patients with chronic periodontitis

Chronic periodontitis (CP) is a multifactorial disease and the most common type of periodontitis mainly caused by microbial plaque. Insufficient oral hygiene may initiate CP and it can be further modified and progressed by environmental and genetic susceptibilities. The aim of the present study was to investigate the association between VDBP (rs7041 and rs4588) and (Taq 1-rs7975232 and Apa1-rs731236) SNPs of VDR gene receptor and susceptibility to CP in an Iranian population. Sixty nine cases with diagnosis of CP and 78 matched healthy controls engaged in this study. Three-milliliter peripheral blood samples were obtained for DNA isolation. Genotype analysis was performed using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Chi-squared test was used for distribution of genotypes analysis. 95% confidence interval (CI) was used to calculate the odds ratio (OR). Deviation from Hardy-Weinberg equilibrium, multiple inheritance models, linkage disequilibrium and haplotype analysis were done. There was no significant association between genotype/phenotype of VDBP's SNPs (rs7041 and rs4588) and occurrence of chronic periodontitis (p value = 0.401) Moreover, no statistically significant association was found between chronic periodontitis and Taq1 (rs731236) (p value = 0.401) and Apa1 (rs7975232) (p value = 0.248). The analysis of alleles and genotypes' distribution between different severities of chronic periodontitis and healthy controls indicated a significant association between various severities of chronic periodontitis and Apa1 (rs7975232) (p value = 0.011) and VDBP's SNPs (rs7041 and rs4588) (p value = 0.038), whereas no statistically significant association was observed between various severities of chronic periodontitis and Taq1 (rs731236) (p value = 0.278). Our results suggest a significant association between severity of chronic periodontitis and Apa1 (rs7975232) and VDBP SNPs (rs7041 and rs4588). Sequencing studies on different populations may release other results due to the genetic and racial diversity.

Interleukin-2, -16, and -17 gene polymorphisms in Iranian patients with chronic periodontitis.

Chronic periodontitis (CP) is a multifactorial disease and the most common type of periodontitis mainly caused by microbial plaque. CP can be brought on by, and progresses with, insufficient oral hygiene, and environmental and genetic susceptibilities. The aim of the present study was to investigate the association between interleukin (IL)-2 (T-330G), IL-16 (T-295C), and IL-17 (A-7383G) gene polymorphisms and the susceptibility to CP in an Iranian population. Ninety-nine cases diagnosed with CP and 75 matched healthy controls engaged in the present study. 3cc peripheral blood samples were obtained for DNA isolation. Genotype analysis was performed using restriction fragment length polymorphism polymerase chain reaction. Genotype distribution and allele frequencies within groups were compared using χ2 -test, and logistic regression analysis was used to recognize the independent relation between the disease and the absence or presence of alleles. There was no polymorphism in IL-2 (T-330G) among our patients, and the TT genotype was present in both study groups. Moreover, none of the studied genotypes and alleles of IL-16 (T-295C) and IL-17 (A-7383G) was significantly associated with CP. The present study demonstrated no association between IL-2 (T-330G), IL-16 (T-295C), and IL-17 (A-7383G) genotypes and CP in an Iranian population.

Determination of ETS1 gene single nucleotide polymorphism in Iranian patients with ankylosing spondylitis

Ankylosing spondylitis (AS) isan inflammatory arthritis with unknown etiology. AS mostly affects the axial skeleton and peripheral joints. The genetic contribution is believed to be a major attributable reason of overall susceptibility to AS. ETS1, also known as the avian erythroblastosis virus E26 (v-ets) oncogene homolog-1 gene, is essential in the development of immune cells in both adaptive and innate immunity. This study investigated the association of single nucleotide polymorphisms (SNPs) in the ETS1 gene (rs1128334 and rs10893872) with ankylosing spondylitis in Iranian population. The study samples comprised 495 AS patients and 490 controls. All samples were selected from the Iranian population. Two SNPs were chosen from the ETS1 gene (rs1128334 and rs10893872), and their association with AS was examined by applying the Real-time PCR allelic discrimination method. The results showed no significant associations between rs1128334 and rs10893872 SNPs and the risk of AS. However, the association between rs10893872 and the Bath Ankylosing Spondylitis Functional Index (BASFI) was significant (p=0.02) after Bonferroni correction, while BASFI was significantly increased in cases with CT in comparison to CC genotype. The results of this study on the Iranian population did not confirm the association of the ETS1 gene SNPs with AS susceptibility; however, the association was significant in Han Chinese populations. The diversity in results among different populations is common in gene association studies of multifactorial diseases. Further investigations will be needed to identify other risk variants of the ETS1 genewhich are correlated with AS susceptibility.

PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus

ABSTRACTBackground: PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease.Objective: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene.Methods: The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene.Results: Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs.Conclusions: The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases.

Analysis of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligand genes polymorphisms in Iranian patients with systemic sclerosis

Genetic factors have a great role in the pathogenesis of autoimmune diseases by cooperating with environmental stimuli. Killer immunoglobulin-like receptors (KIRs) are cell surface proteins on NK cells whose association with major histocompatibility complex-I regulates their killing function. The aim of this study was to provide information on the possible association between KIR and human leukocyte antigen (HLA) genes with systemic sclerosis disease in Iranian population. A total of 279 systemic sclerosis patients and 451 healthy controls were enrolled in this case-control study in order to determine the presence or absence of 19 KIR genes and 6 specific HLA class I ligands. DNA was analyzed by polymerase chain reaction using the specific sequence primer method (PCR-SSP). Among 11 discovered KIR genotypes, 6 genotypes showed a considerable role and 4 genotypes could preclude the risk of systemic sclerosis (SSc) disease. The gene-gene interactions were also analyzed, and significant confounding effects were seen between involved genes in these two combinations: "KIR3DL1; HLA-BW4-Thr80" and "KIR3DL1 -HLA-BW4-A1." None of single KIR genes showed significant effect on the risk of SSc. We conclude that there is an important relationship between KIR genes and their HLA ligands with incidence rate of systemic sclerosis in Iranian population. The powerful role of a number of discovered KIR/HLA compounds such as activating KIR genotype 3 and HLA-BW4-A1 confirmed the provocative hypothesis of the interplay between activating or inhibitory KIR genes with HLA ligands as a critical index of systemic sclerosis predisposition.

No association between ITGAV rs3738919 and rs3768777 polymorphisms and rheumatoid arthritis susceptibility in Iranian population

Abstract Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by angiogenesis, cell proliferation and bone and cartilage damage in the affected joint. Many genetic and environmental factors contribute to RA susceptibility. ITGAV is a member of the integrin family, which plays a major role in bone destruction, angiogenesis and macrophage-dependent inflammation and has been suggested that it may be an RA susceptibility gene. In this study, we investigated association of two single nucleotide polymorphisms in ITGAV (rs3738919 and rs3768777) with susceptibility to RA. Methods: Iranian patients with confirmed RA, aged over 50 years, were compared with healthy controls for allelic and genotypic frequencies of these polymorphisms. The subjects and controls were matched through their race, age and sex. After whole genome extraction, we compared genotype frequencies of analyzed alleles in RA patients and controls using a polymerase chain reaction (PCR)-restriction fragment length polymorphism assay. Association of rs3738919 and rs3768777 with RA was tested in these two sample sets using the χ2-test. Results: Statistical analysis indicated no association between RA and rs3738919 allele frequencies (C and A alleles), single genotype frequencies (AA, AC, CC) and combined genotype frequencies of (AC+CC vs. AA). We also found no evidence of association between rs3768777 SNP allele frequencies, single genotype frequencies and combined genotype frequencies and RA susceptibility. Conclusions: This study did not find any association between RA and ITGAV rs3738919 and rs3768777 polymorphisms in Iranian patients. However, this finding is not conclusive due to the limited sample size. A subsequent study with a larger sample size is recommended.

Chitotriosidase Activity and Gene Polymorphism in Iranian Patients with Gaucher Disease and Sibling Carriers.

Chitotriosidase (CT) activity is a useful biomarker for diagnosis and monitoring of Gaucher disease (GD). Its application is limited by some variants in the CT gene. Two main polymorphisms are 24 bp duplication and G102S led to reduce CT activity. The aim of this study was to determine these variants influencing on plasma CT activity. Blood samples were collected from 33 patients with GD, 15 sibling carriers and 105 healthy individuals serving as controls. CT activity was measured using 4-methylumbelliferyl-β-D-N,N',N″triacetylchitotrioside substrate in plasma samples. The CT genotypes of 24 bp duplication and G102S variants were determined using PCR and PCR-RFLP. Untreated GD patients had a significantly higher CT activity compared to treated patients (P = 0.021). In addition, chitotriosidase activity in carriers was higher rather than controls. Allele frequencies of 24 bp duplication in GD patients, sibling carriers and controls were 0.21, 0.266 and 0.29 and for G102S were 0.318, 0.366 and 0.219, respectively. Different G102S genotypes had not significant effect on CT activity. Chitotriosidase activity has a positive correlation with age in normal group, carriers, and negative correlation with hemoglobin in GD patients. Using cut-off level of 80.75 nmol/ml/h, sensitivity and specificity of CT activity were 93.9% and 100%, respectively. Chitotriosidase activity is a suitable biomarker for diagnosis and monitoring of GD. Determination of 24 bp duplication is helpful for more accurate monitoring the GD patient's therapy. However, it seems that, specifying of the G102S polymorphism is not required for Iranian GD patients.

Analysis of killer cell immunoglobulin-like receptors and their human leukocyte antigen-ligands gene polymorphisms in Iranian patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease. Natural killer (NK) cells play a critical role in the pathogenesis of autoimmune disorders that mainly express killer cell immunoglobulin-like receptors (KIRs). The present study was undertaken to determine the association of the KIR alleles, genotypes, and KIR-human leukocyte antigen (HLA) ligand gene combinations with the susceptibility to SLE. The genotyping of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method. The study population consisted of 230 SLE patients and 273 ethnical-, age-, and sex-matched healthy controls. The association of the polymorphisms with the prevalence of 11 clinical criteria in patients was analyzed. The carrier frequency of HLA-A-Bw4 was modestly decreased in the SLE patients. The prevalence of hematological and renal disorders was significantly increased in patients with combination of KIR3DL1(+); HLA-B-Bw4(Thr80+) and KIR2DS1(+); HLA-C2(+) genes, respectively. Female patients with combination of KIR2DL2(+); HLA-C1(-) genes were more likely to develop serositis. In addition the prevalence of renal disorders, oral ulcer and serositis was significantly increased in male patients with KIR3DP1(+), KIR2DS1(+), and KIR2DS3(+) genotypes respectively. Our results showed that the presence of activating KIR receptors alone or in combination with their HLA ligands and the absence of inhibitory KIRs in combination with their HLA ligands may activate NK cells and are significantly correlated with the prevalence of renal disease, hematologic disorders, serositis, and oral ulcer in SLE patients.

Evaluation of Long Stress-Induced Non-coding Transcripts 5 Polymorphism in Iranian Patients with Bladder Cancer

Evaluation of Long Stress-Induced Non-coding Transcripts 5 Polymorphism in Iranian Patients with Bladder Cancer