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Background: There are citrullin peptides in Rheumatoid Arthritis (RA) patients that are changed by Peptidyl Arginine Deiminase enzymes (encoded by PADI genes). An association between RA and PADI-4 haplotypes has been reported by researchers. The aim of this study is evaluation of PADI-4 Gene polymorphism in patient with Rheumatoid Arthritis referring. Methods and Materials: In this cross-sectional study we extracted the genomic DNAs from the whole blood samples of 50 patients with RA ( on the basis of ACR criteria) referring to Emam Reza hospital in Mashhad and a control group involving 50 healthy khorrasanian participants. DNA genom was extracted with nonenzymatic salting out method. Genotypes were determined by PCR simple sequence specific primers (PCR-SSP). Data were analyzed with Chi-Square and Fisherexact Test. Results: 58% of the patients had genotypes of 1and 2 38%: 1,4, 2%: 1b,2 ,and 2%: 2,4 .In the control group, 72% had genotype 1,2 22%: 1 and 4, 6%: 1b,2 while none of them had genotype 2,4. Conclusion: There was not any significant relationship between the presence of different PADI-4 genotypes and RA in Khorrasanian population

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Background: Leishmania major and leishmania tropica are the main causes of cutaneous leishmaniasis in Iran, especially in Isfahan and Bam regions. In this study, noticing the effect of diversity of this parasite strains on designing disease control strategies, human isolates were examined through PCR-RFLP to determine the type of strains. Materials and Methods: In this experimental study, 340 samples obtained from CL patients due to Leishmania were cultured and prepared for microscopic study and examined through PCR-RFLP. The products of some of these samples were sequenced and analyzed. ITS1 region of genomic DNA was extracted and amplified with LITSr and L5.8s primers. Data on sequencing the samples were related to ITS1 region that in extracted DNAs with LITSr and L5.8s primers appeared with four kinds of genotype patterns, two for L.major and two for L.tropica in Isfahan and Bam regions. Results: Genotypic groups, LmA and LmB, were detected from L.major isolates while LtA and LtB genotypic groups were indicated for L.tropica in these two regions. The most prevalent genotypes related to isolates of Isfahan were LmA geneotype, whereas LtA geneotype was mostly reported in isolates of Bam. Conclusion: Leishmania major and leishmania tropica, the causative agents of zoonotic cutaneous leishmaniasis (ZCL) in Isfahan and anthroponotic cutaneous leishmaniasis (ACL) in Bam, respectively, are genetically polymorphic species. There exists a relationship between genetic heterogeneousness and clinical manifestation and geographical regions of this disease in human

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Background: Programmed death 1 (PDCD1), a negative T-cell regulator which induces peripheral tolerance, belongs to Ig super and CD28/CTLA-4 families. PD-1 gene induces negative signals in T-cells during interaction with its ligands. Thus the aim of this study was to investigate the relationship between PD-1 polymorphism and the risk of rheumatoid arthritis (RA) in Iranian patients and healthy controls. Materials and Methods: In this case-control study, genomic DNA was extracted from the whole blood samples using DNA purification kit (DNG-plus, Cinnagen, Iran). PD1.1G/A as a SNP located on promoter with position -536 were genotyped for 120 RA patients and 188 healthy controls through PCR-RFLP method. Association of genotypes and alleles frequency in the patients was compared with controls and analyzed using Chi-square test and 2×2 contingency table in SPSS software version 15.0. The diagnosis of RA patients and provision of their clinical information was done in Rheumatology Research Center of Tehran University of Medical Sciences, Tehran, Iran. Results: The A allele of the PD1.1 polymorphism located on the promoter of PD-1 gene was significantly more frequent in Iranian RA patients than the controls (p=0.04). There were no significant differences in PD1.1G/G genotype (p=0.08), PD1.1A/A genotype (p=0.39), and PD1.1G/A genotype (p=0.16) between RA cases and controls. Conclusion: The findings of this study showed the presence of a significant relationship between the A allele of the PD1.1 (-536) of the promoter and susceptibility to RA in Iranian patients.

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Background: Multiple sclerosis (MS) is an autoimmune disease which demyelinates the central nervous system. Vitamin D, is a potential environmental factor which influences this disease. The majority of the biological activities of the polymorphism forms of vitamin D are done through its receptor gene (VDRG). The aim of this study was to examine the relationship between BsmI polymorphisms in VDRG and the incidence of MS. Materials and Methods: In this case-control study, the BsmI polymorphism in the VDRG was studied in 80 Iranian MS patients and 50 healthy controls of the same genetic background and age through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method Results: There was a significant difference in the frequency of BsmI VDRG polymorphism genotypes between MS patients and controls (P=0.023). Conclusion: This study indicated that the VDRG BsmI polymorphism is associated with MS in this population.

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Background: In addition to known environmental and acquired factors effective in cardiovascular diseases, polymorphisms of VKORC1 and CYP2C9 genes are identified as the main genetic factors involved in warfarin dosage requirement variations in these patients. With this approach, investigating the frequency of 1639 G>A in VKORC1 gene for determining the specific dosage required for each person was the main aim of this study. Materials and Methods: In this experimental study, peripheral blood samples were obtained from 200 patients with cardiovascular disorders in the northwestern areas of Iran (West and East Azarbayjan and Ardabil) and RFLP-PCR technique was used to determine the 1639G> A polymorphism of VKORC1. Results: Using Hardy-Weinberg law‏, polymorphism amounts of 1639G> A gene from VKORC1 in female and male patients with normal, heterozygote, and homozygote were determined 21.6%, 53.7%, 24.5% , and 22.3%, 60.6%, and 17.02% , respectively. Conclusion: VKORC1 genotyping is one of the important parameters that together with other confounding factors reduce the role of trial and error in patients with cardiovascular diseases. Genotypic variety and the high frequency of allele A in the studied population can justify varied responses to warfarin therapy and the importance of investigation before starting treatment with warfarin.

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Background: Chronic hepatitis B virus (HBV) infection is a multi-factorial disease that is accompanied with serious clinical complications. Host’s genetic background, especially immune–genetic factors, is critical in the pathogenesis of infection. Gamma interferon ((INF-γ) and its receptor have an important role in immune response to the virus and clinical course of the disease. The aim of this study is to investigate the association between single nucleotide polymorphism -611G/A located in promoter of gamma interferon receptor1 gene (INFGR1) and chronic HBV infection. Materials and Methods: In this Case Control study, genomic DNA from peripheral blood samples of 150 chronically HBV infected patients and 150 healthy controls was extracted by phenol-chloroform method. DNA analysis was performed by PCR-RFLP method and P<0.05 was considered significant. Results: After stages of genotyping and statistical analysis, a significant difference was observed between patient and control group, so that genotype GG was higher in the control group compared to the patient group. Conclusion: The host’s immune-genetic background can play an important role in the pathogenesis of infectious disease. Variations in INFGR1 were related to several diseases. The results showed that the presence of GG allele is accompanied by a decrease in susceptibility to chronic HBV infection.

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Background: IFN-&lambda3 (IL-28B) is a new cytokine from the type III interferons. Its role in several biologic activities, such as regulation of immune responses, tumor and metastasis, or its functions in HBV and HCV diseases, has been shown. The present study evaluated the frequency of rs8099917 allele polymorphism in IFN-&lambda3 gene in Iranian population.

Materials and Methods: In this laboratory-experimental study, after collecting blood samples from 118 unrelated Iranian subjects, DNA extraction was performed according to the kit protocols. Evaluation of rs8099917 allele polymorphism was done by Nested-PCR and RFLP method using BsrDI and Tsp451 restriction enzymes.

Results: After running the tests and data analysis, the frequencies of GG genotype (2.5%), GT genotype (31.4%), and TT genotype (66.1%) were obtained. Allele frequencies were 71.22% for G allele and 81.78% for T allele.

Conclusion: The results of this study showed that TT genotype and T allele are the dominant frequencies of rs8099917 allele of IFN-&lambda3 gene in Iranian population. Regarding the different established functions of IFN-&lambda3, frequency determination of this variant can be helpful in different studies, designs, evaluations, and treatment procedures in some diseases, such as tumors and hepatitis, in Iranian patients.

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Background: There is abundant evidence indicating that inflammatory mechanisms within the central nervous system contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current study BAT1 -22 promoter polymorphism was analyzed in AD and control subjects.

Materials and Methods: In this case-control study, genomic DNA from peripheral blood samples of 153 Alzheimer’s patients and 153 healthy controls was extracted using salting-out method. DNA analysis was performed by PCR-RFLP method and p<0.05 was considered statistically significant.

Results: After genotyping and statistical analysis the results failed to show any association between BAT1 -22 promoter polymorphism and sporadic Alzheimer’s disease.

Conclusion: BAT1 -22 is not associated with Alzheimer’s disease in Iranian population and so has no effect on predisposition to sporadic Alzheimer’s disease.

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Background: Preeclampsia (PE) is a serious problem of pregnancy and its etiology is still unknown. The inheritance of preeclampsia is one of the theories regarding to the etiology of preeclampsia. Methylenetetrahydrofolatereductase (MTHFR) is a key enzyme in folate metabolism and the C677T polymorphism of the MTHFR gene is associated with decrease MTHFR activity, and therefore cause higher blood levels of homocysteine and leads to vascular disease that can be the reason of preeclampsia. The aim of this study was to evaluate the relationship between MTHFR gene C677T polymorphism with PE development in south-west of Iran.

Materials and Methods: This case-control study was performed in 129 preeclamptic pregnant women and 125 control individuals.The C677T polymorphism of the MTHFR gene was determined by PCR-RFLP method.

Results: The CC, CT and TT genotypes frequency of C677T polymorphism of MTHFR gene were 57.4, 38.8 and 3.9 percent in preeclamptic women and 53.6, 40 and 6.4 percent in control group. They were not significantly different (p=0.614). However, the frequency of TT genotype was higher in control group (p=0.36). There was not any significant difference in T allele distribution between preeclamptic women (23.3%) and control group (26.4%).

Conclusion: Our results showed that there was not any correlation between the C677T polymorphism and PE but the TT genotype of C677T polymorphism seems to be a protective factor for preeclampsia.

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Background: Schizophrenia is a widespread neurodegenerative disorder, which affects approximately 1% of the world population. It is a multifactorial and a highly heritable disease to which genetic factors contribute up to approximately 80%. Nowadays, multitude of genes have been discovered that relate to this disorder mostly by affecting the performance and levels of neurotransmitters in neural systems. Since PAI-1 is a considerable gene in the performance of neural systems, the present study dealt with the relationship between -675 4G/5G polymorphism in PAI-1 gene and schizophrenia among Iranian patients.

Materials and  Methods: This case-control study was carried out on 106 blood samples collected from individuals suffering from schizophrenia and 122 healthy controls. DNA was extracted from the samples and the frequency of the polymorphisms was analyzed using ARMS-PCR method. Finally, the products were detected on 2% agarose gel electrophoresis.

Results: The analysis of the data for -675 4G/5G polymorphism showed that 17.9% of the patients and 1.6% of the controls were mutant homozygous and 65.1% of the patients and 45.9% of controls were heterozygous. Also, 17% of the patients and 52.5% of the controls were normal homozygous.

Conclusion: There was a significant relationship between PAI-1 4G/5G polymorphism and the incidence of schizophrenia. To the best of our knowledge, this is the first study in Iran that assesses the frequency of the polymorphism among Iranian patients. However, further studies with more samples are necessary.

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Background: Interleukin-16 (IL16) is an important regulator of T cell activation and was reported to act as achemo-attractant agent. There are evidences that IL16 can control the neuroinflammatory processes in Alzheimer’s disease (AD). This study was performed to show whether the IL-16 genepolymorphism, rs11556218 is associated with the risk of sporadic AD in Iranian population.

Materials and Methods: Totally, 148 AD patients and 137non-dementia controls were recruited in this case-control study. Genotyping of rs11556218 T/Gpolymorphism was performed by PCR-RFLP method using the NdeI restriction enzyme.

Results: Statistical analysis of rs11556218 genotypes showed a protective effect against AD in the heterozygote genotype (p=0.001, OR=0.16(0.1-0.28)). Frequency of rs11556218 allele T was higher in patients than controls (p=0.001, OR=0.32(0.21-0.49)).

Conclusion: Our results indicate thatrs11556218 polymorphism has a protective role in the development of sporadic AD in Iranian population.

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Background: Nitric oxide is synthesized in endothelial cells by eNOS and acts as a pleiotropic regulator involved in carcinogenesis. Most gastric cancers develop from stomach epithelial cells therefore, NO may play a role in their development. Polymorphisms of eNOS have been shown to be associated with cancer susceptibility. In the present study, we investigated the association of the eNOS genotypes with gastric cancer risk in Guilan Population.

Materials and Methods: In this case-control study, we analyzed the Glu298Asp polymorphism of eNOS in 87 patients with gastric cancer and 90 healthy controls. The genotyping of eNOS polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism assays. All statistical analyses were conducted by the MedCalc statistical software.

Results: No association between the eNOS genotypes and gastric cancer risk was found. Among the 87 patients, 45 had Glu/Glu, 38 were Glu/Asp, and 4 were Asp/Asp. In the control group, 44 had Glu/Glu, 40 were Glu/Asp, and 6 were Asp/Asp. We found no significant differences in allele and genotype frequencies between control and patient specimens.

Conclusion: We found that there was no association between this polymorphism and gastric cancer risk. Results suggest that eNOS polymorphism may play a role in inhibition of gastric cancer. However, larger population-based studies are needed for clarifying the role of eNOS polymorphism in gastric cancer.

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Background: Diabetic retinopathy (DR) is a severe complication of diabetes and the leading cause of blindness among working adults worldwide. Chronic extra cellular hyperglycemia in diabetes stimulates reaction oxygen species (ROS) production and increase oxidative stress. Glutathion S- transferases (GSTs) enzymes have been shown to protect human from reactive oxygen compounds damage. The aim of the present study was to investigate whether the genetic polymorphism of GSTP1 is associated with DR.

Materials and Methods: This case–control study, included 70 patients with DR and 70 healthy volunteers. Genomic DNA was extracted from peripheral blood leukocytes. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Statistical analysis was performed using the MedCalc program for Windows version 12.

Results: The prevalence of genotype frequencies of the GSTP1 Ile/Ile and Ile/Val were 71.42% and 28.57% respectively, in DR subject, whiles in healthy volunteers were 78.58% and 21.42%, respectively. Statistical analysis has not emerged significant difference from the comparison of either genotype (&Rho>0.05).

Conclusion: There was no evidence that GSTP1 variants were associated with DR in studied population. Further research is required to clarify role of GSTP1 in DR.

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Background: Infertility is a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse. Male infertility affecting 15% of couples. Environmental and genetic factors are involved in male infertility. Paraoxonase (PON) is an antioxidant enzyme which plays an important role in various diseases and is associated with oxidative stress and lipid metabolism. The PON gene family consists of 3 genes, PON1, PON2, and PON3, that located on the long arm of chromosome 7. In this study, the association of PON1 gene polymorphism at position 192 Q/R with idiopathic male infertility were investigated.

Materials and Methods: Blood Samples were collected from 120 patients diagnosed with idiopathic male infertility and 124 control subjects, and genotyped by PCR-RFLP method. To estimate the association between genotype and allele frequencies in cases and controls, P-values were assessed by Chi-square (&chi2) analysis.

Results: We observed a significant difference in genotype distributions of PON1 192 Q/R polymorphism between patients and controls (P= 0.0001). Our findings revealed individuals with the variant QR and RR had a significant decrease risk of idiopathic male infertility (RR: OR= 0.057, 95%CI=0.003-1.08, P= 0.05. QR: OR= 0.288, 95%CI= 0.132-0.394, P= 0.0001).

Conclusion: Our data indicate that the PON1 192 Q/R polymorphism maybe associated with decreased risk of idiopathic male infertility. Although more studies should be considered with larger number of patient and control subjects to confirm our results.

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Background: Rheumatoid arthritis is a chronic inflammatory disorder that mainly affects the peripheral joints and surrounding tissue. Genetic and environmental factors have important roles in pathogenesis. The role of oxidative stress and the enzymes involved in the pathogenesis of rheumatoid arthritis have been studied in these years. A predominant role in counteracting reactive oxygen spieces is played by endogenous antioxidant enzymes, and glutathion peroxidase (GPx). An alteration of CTC codon to CCC codon which results in substitution of leucine instead of proline in 198th amino acid location is one of the important polymorphisms of this gene. The aim of this study was to evaluate the association of GPx1 gene polymorphism in patients with rheumatoid artheritis.

Materials and Methods: The case-control study included 130 patients with rheumatoid artheritis and 126 healthy individuals. Genomic DNA was extracted from white blood cells and the genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP). Statistical analysis was carried using the MedCalc (version 12.1).

Results: The frequencies of CC, CT and TT genotypes of GPx1gene were 32.31%, 43.08% and 24.61% respectively, in rheumatoid arthritis patients, whiles in healthy volunteers were 42.62%, 54.10% and 3.28%. Statistical results showed significant relationship between TT genotype of GPx1 gene and Rheumatoid arthritis (p=0.002, &chi2 =11.715, OR: 9.90 95% CI (2.04 to 48.01)).

Conclusion: In conclusion, these results indicate that TT genotype of GPx1 gene may be associated with the risk of rheumatoid artheritis in the studied population. However, further research is required to clarify the role of gene polymorphism in rheumatoid arthritis.

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Background: Allergic rhinitis, a chronic inflammatory disease of the respiratory tract, includes an IgE-mediated inflammatory response in the mucosal region of the aerial tubles. Since IL-8 plays a role in increasing the amount of immunoglobulin E and serves as an effective factor in the prevalence of this disease, so this study aims to investing at that whether IL-8 genotypes of 133 C/G polymorphism is associated with the amount of immunoglobulin E in serum in patients with allergic rhinitis.

Materials and Methods: In this analytical and descriptive study, by investigating 130 patients with AR and 62 healthy control volunteers in Chahar Mahalo Bakhtiari province, total level of IgE in serum was determined by ELISA method and then its association with 133 C/G polymorphism was investigated. T-test and chi-square statistical analyzes were performed using SPSS software for statistical analyses.

Results: the total serum IgE level of the patients with GC genotype of 133 C/G SNP were significantly higher regarding normal individuals (p<0.05).

Conclusion: The sigmificant relationship between 133 C/G genotype in IL-8 P gene promoter and increased serum IgE level confirms tht it plays a role in the prevalence of AR.

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Background: Estrogen hormone regulates cell proliferation in breast tissue physiologically. Evidences show that changes in estrogen signaling pathways, including the receptor alpha (ER&alpha), happen during breast cancer progression. ER&alpha is expressed in most breast tumors and its association with the development of low-grade tumors has been demonstrated. Single nucleotide polymorphisms (SNPs) in genes may differ in susceptibility to cancer and result in different respond to treatment in different populations. The present study aimed investigated the association between single nucleotide polymorphisms (rs2234693: C/T) in gene ESR&alpha in patients with breast cancer.

Materials and Methods: In this case-control study 150 women with breast cancer and 142 healthy women without a family history of breast cancer were enrolled. DNA was extracted from blood samples. After primer design, technique of PCR-RFLP was used and samples were genotyped by acrylamide gel electrophoresis. Statistical analyzes were performed using SPSS version 20 and chi square test and Final findings were specified.

Results: TT and CT genotypes for ra2234693: C/T site compared with the CC had 5.5 and 1.5-fold increased risk respectively. Statistically significant differences were found between cases and controls for fibrocystic disease and age at menarche.

Conclusion: We not found an association between C/T polymorphism and breast cancer. But CC and TT genotypes of this polymorphism in estrogen receptor alpha gene related with breast cancer that are consistent with the findings of some other researchers.

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Background: Nowadays, the decline in birth rate is one of the most important social problems in developing societies. Infertility is defined as a failure to conceive in a couple trying to reproduce after one year of regular intercourse without contraception. Leptin have been implicated in maintaining normal female reproductive functions, including lactation, folliculogenesis, ovarian steroidogenesis, the maintenance of mammary gland morphology, the development of dominant follicles and oocytes, the maturation of the uterus endometrium, and menstrual cycle regulation. Sinyle-nucleotide polymorphism T>C found in exon 3 leads to substitution of Arg>Trp at codon 1.5 (R105W). In this case-control study, we aimed to evaluate the association of this polymorphism and the risk of female infertility in the population of Guilan.

Materials and Methods: Blood Samples were collected from 86 patients diagnosed with female infertility and 60 control subjects, and genotyped by allele-specific PCR (AS-PCR). To estimate the association between genotype and allele frequencies in cases and controls, Chi-Square analysis was used.

Results: Analysis revealed no significant differences were found in genotype and allele distributions of LEP Arg105Trp between infertility cases and controls (p=0.21, p=0.2) in this population.

Conclusion: Our findings indicated no significant association between the Arg105Trp polymorphism and female infertility risk (p=0.21). While, more studies are needed to confirm the results.

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Background: Breast cancer is the most common cancer and one of the main causes of cancer-related death all over the world that has become a major public health concern. Human apurinic/apyrimidinic endonuclease (ApE1) is a multifunctional protein that has an important role in the base excision repair (BER) pathway. Single- nucleotide polymorphism T>G found in exon 5 led to substitution of Asp>Glu at codon 148 (Asp148Glu). In this case-control study, we aimed to evaluate the association of this polymorphism on the risk of breast cancer in Guilan population.

Materials and Methods: To study gene polymorphism APE1 (Case- Control), blood samples were collected from 75 patients diagnosed with breast cancer and 75 control subjects, and genotyped by allele-specific PCR (AS-PCR). To estimate the association between genotype and allele frequencies in cases and controls, Chi-Square analysis was used.

Results: Analysis revealed no significant differences were found in genotype and allele distributions of ApE1 Asp148Glu polymorphism between breast cancer patients and controls (p=0.1, p=0.6 respectively) in this population.

Conclusion: Data from this study indicated no significant association between the Asp148Glu polymorphism and breast cancer risk (p=0.1). Further study is needed to clarify the impact of Asp148Glu polymorphism on the breast cancer.

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Background: The pathogenesis of recurrent pregnancy loss includes complex interaction of several genetic and environmental factors. Changes in blood coagulation factors during pregnancy may play an important role in the occurrence of recurrent abortions (RA). Recently, inherited thrombophilia has been considered as a possible cause. Therefore, in this study we have investigated association of factor V (G1691A) and factor II (G20210A) polymorphisms in Iranian patients with recurrent abortions.

Materials and Methods: A total of 203 women participated in this study: 105 women with two or more consecutive unexplained miscarriage as cases and 98 women with at least two healthy children as control group. Total genomic DNA was isolated from Peripheral blood leukocytes. The presence or absence of mutation in the FV (G1691A) and FII (G20210A) polymorphisms were assessed by PCR-RFLP, using Mnl1 and HindIII digestion enzymes, respectively. Finally, the data were  analyzed using Chi-Square test.

Results: The results showed no statistical significant differences in the prevalence of FV (G1691A) and FII (G20210A) polymorphisms between patients and control group.

Conclusion: considering the results of this study, these polymorphisms Seem to have no role in etiology of recurrent pregnancy loss in the studied population.