Background: Hypertrophic cardiomyopathy (HCM) is a various collection of heart diseases with autosomal dominant inheritance affecting 0.2% of the global population. HCM is also the most common cause of sudden cardiac death in individuals younger than 35 years old. Approximately, 40% of affected cases are associated with MYBPC3 gene. The aim of this study is to investigate the possible presence of mutation in 15 and 18 exons of MYBPC3 gene in patients with HCM in Chaharmahal Va Bakhtiyari province.

Materials and Methods: In this experimental study, 30 HCM patients were selected. DNA was extracted using standard phenol-chloroform method. Certain exons were amplified by PCR method. And then, SSCP and HA methods were run.

Results: Significant differences were observed between the positive control samples and other samples. However, there were no difference in studied exons or shift in the bands.

Conclusion: Mutations in the exons of MYBPC3 gene may cause the HCM disease, and change in other exons may be the causative agent in this geographical region and change in this studied exons may not have contributed to the HCM disease. However, it is necessary to study more patients for getting a better conclusion.

  Background: Approximately, 50% of male infertility causes have remained unknown. It seems that genetic disorders may lead to many cases of idiopathic infertility. XRCC1 ( X-ray Repair Cross Complementing group 1) acts as a scaffolding protein in the base excision repair (BER) and single strand break repair (SSBR). Single nucleotide polymorphisms (SNP) of XRCC1 may influence DNA repair capacity. Thus, they had been considered as a risk factor for infertility. XRCC1 Arg399Gln polymorphism was located on p rotected domain , BRCT1 . The aim of this study was to explore the p ossibility of association between XRCC1 Arg399Gln polymorphism and susceptibility to idiopathic male infertility.

  Materials and Methods: In this case-control study, the genotype and allele frequencies of Arg399Gln polymorphism were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on a Guilanian population consisting of 144 men with idiopathic infertility and 166 healthy men. Statistical analysis was performed using the MedCalc 12 software.

  Results: According to our results, compared with Arg/Arg genotype, the Arg/Gln , Gln/Gln and Arg/Gln + Gln/Gln genotypes showed a significant association with an increased risk of idiopathic male infertility ( OR=4.19 95%CI 2.37-7.41, p<0.0001 ), (OR=3.42 95%CI 1.50-7.81, p<0.0034), (OR=4.06 95%CI 2.32-7.09, P<0.0001) , respectively. In addition, the Gln allele frequency in patients was significantly higher than that in controls(p=0.0004).

  Conclusion: In total, Arg399Gln polymorphism of XRCC1 gene can be associated with male infertility and Gln allele might be a risk factor of idiopathic male infertility in in this sample population. Larger population and different ethnicities should be studied to achieve a definitive conclusion.

  Background: In spite of designing and applying an effective vaccine against Hepatitis B virus (HBV), chronic infection with this virus is still one of the most important health problems worldwide. Host genetic background including single nucleotide polymorphisms play a significant role in chronicity or clearance of the infection. The final product of programmed cell death 1 gene (PDCD1) is expressed frequently on T-cells and in chronic viral infections, prevent the virus-specific T-cell response against the virus. In this study, the association of a single nucleotide polymorphism (+7146A/G) in intron 4 of PD1 gene with chronic hepatitis B infection in Iranian population has been assessed.

  Materials and Methods: 212 chronic HBV patients and 208 healthy controls were analyzed in this case-control study. Genomic DNA of the studied individuals was extracted and after performing polymerase chain reaction (PCR), polymorphism of +7146 was determined via RFLP method.

  Results: Frequencies of GG, GA and AA genotypes on position 7146 of the intron 4 of PD1 gene were 77.4%, 20.7% and 1.9% in patient group and 80.8%, 15.4% and 3.8% in control group, respectively. After statistical analysis, No significant difference was observed between patient and control groups (p=0.198).

  Conclusion: Genotype frequencies in the studied population are in accordance with the results of previous studies. Results of the present study suggest that there is not any association between A/G single nucleotide polymorphism in intron 4 of PD1 gene and susceptibility to chronic hepatitis B in Iranian population.

Background:  Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more consecutive pregnancy losses prior to 20^th week of gestation. There are several leading causes of RPL including uterine anatomical defects, infections, genetic, immunological, and environmental factors. However, despite in a large number of cases no causes have been identified, therefore, it is introduced as idiopathic.

Recent studies have implicated the role of miRNAs in endometriosis, preeclampsia, infertility and RPL. Therefore, the aim of the present study was to investigate the association of miR-196a2C>T (rs11614913) with RPL in Iranian women.

Materials and Methods: In this case-control study, 183 Iranian women including 83 patients with at least two unexplained consecutive pregnancy losses and 100 healthy controls with at least one live birth and no history of pregnancy loss were investigated. Patients with recurrent pregnancy losses due to anatomic, hormonal, chromosomal, infectious, autoimmune, or thrombotic causes were excluded from the study group. Genotyping was performed using Tetra- ARMS PCR method.

Results:  Significant difference in distribution of miR-196a2 rs11614913 genotypes was found in RPL patients in comparison to controls, with p value of 0.04 and odds ratio equal to 2.96 (95% CI: 1.03-7.03).

Conclusion: The results of the present study provide evidence for association between genetic variation in miR-196a2 and recurrent pregnancy loss. Further studies will be required to validate the significance of the studied genetic variation in diverse populations and its regulatory role on target genes.

Background: Obesity is a complex, multifaceted disease resulting from a combination of genetic, environmental, and lifestyle backgrounds, and is associated with increased risk of diseases, such as hypertension, dyslipidemia, and type 2 diabetes. MiRNAs have been reported to be associated with chronic diseases such as obesity. The present study is the first investigation that examines the possible association of rs2910164 polymorphism in mir-146a gene with overweight and obesity in Iranian women.

Materials and Methods: This case-control study was conducted on 133 overweight, 75 obese and 173 healthy control women with normal weight. The rs2910164 polymorphism genotypes of mir-146a gene were determined by the Tetra-ARMS PCR method. Also, logistic regression analysis was used to estimate the association between genotypes and obesity risk.

Results: There was a significant association between GC (OR: 1.8, 95%CI: 1-3.3, p: 0.04) and CC (OR: 4.5, 95%CI: 1.6-12.6, p: 0.004) genotypes with susceptibility to obesity. In the dominant genetic model of the C allele (comparison between CC+GC vs. GG), CC+GC genotypes were associated with the risk of obesity (OR = 2.1, 95% CI: 1.2–3.7, p= 0.01).

Conclusion: This study showed that mir-146a gene rs2910164 polymorphism is associated with obesity risk and the C allele may act as a dominant allele and increase the obesity risk in Iranian women.

.

Background: Hemophilia A is an X-linked bleeding disorder caused by heterogenous mutations in factor VIII gene that encodes coagulation factor VIII (F8) protein. Due to the high heterogeneity of mutations, large size (186 kb) and structural complexity of the F8 gene, direct mutation analysis is costly and time consuming. Alternatively, linkage analysis using informative polymorphic markers such as single nucleotide polymorphism (SNP) markers has been introduced as a rapid and cost effective method for hemophilia A carrier detection in families with an affected individual. Several SNP markers associated with the F8 gene region have been studied.

Materials and Methods: In this exprimental study, the characteristics of A/T SNP (rs4898352) as an informative marker located in intron 18 of F8 gene region was investigated in Isfahanin population. rs4898352 marker was genotyped using tetra primer ARMS PCR method followed by agarose gel electrophoresis in 140 unrelated control healthy females in mentioned population. New primers were designed for rs4898352 marker using the oligo 7 software. The allele frequency, degree of heterozygosity and Hardy-Weinberg equilibrium were estimated by use of Genepop program. The polymorphism information content (PIC) value was estimated using the Powermarker software.

Results:  The results showed that the allele frequency of rs4898352 polymorphism for A and T alleles was 0.482 and 0.518, respectively. The observed heterozigosity rate was 60%. Analysis of Hardy-Weinberg Equilibrium demonstrated that the Isfahan population was in equilibrium (p>0.05) for rs4898352 marker. Moreover, analysis of PIC value revealed that this marker could be considered as a highly informative marker in the mentioned population.

Conclusion: Together, the data suggested that rs4898352 could be introduced as an informative marker for molecular diagnosis of hemophilia A in Isfahan Population

Background: Infertility is a multifactorial disorder with genetic and non-genomic factors. It is estimated that female infertility factors accounts for more than 40%. Estrogen is one of the effective hormons  in fertility. Its crucial actions on target tissues are mediated via binding to estrogen receptors(ESR). The ESR1 gene is located on chromosome 6q25.1 and encodes α estrogen receptor. The aim of this study was to analysis of ESR1 rs104893956 polymorphism in female infertility.

Materials and Methods: In this case-control study, of 60 infertiles and 55 healthy controls, blood samples were attained. After the extraction of genomic DNA from peripheral blood leukocytes, Allele Specific-PCR (AS-PCR) method was applied for determining the codon polymorphism. Statistical analysis was performed using the MedCalc software (Version 12.1).

Results: The frecuency of T allele was significantly higher in patients (58%) than the controls (44%). There was higher frequency of TT genotype of the polymorphism in patients (18.33%) compared with controls (1.8%). Our findings revealed that the patients carrying the TT genotype had a significant increased risk of infertility.

Conclusion: The results of this study suggests that ESR1 rs104893956 polymorphism may affect the increased susceptibility to female infertility in Guilan province. The results may be different in other genetic pools or large-studied population.

Background: Diabetic retinopathy (DR) is the complication of diabetes mellitus (DM) and causes blindness among adults. Chronic extra cellular hyperglycemia in diabetes stimulates reaction oxygen species ROS production and increases oxidative stress. GPX-1 that was coded by GPX-1 gene is a key enzyme in protecting vessels against oxidative stress. The aim of this study was to evaluate the association of GPX-1 gene Pro 198 Leu polymorphism in patients with diabetic retinopathy.

Materials and Methods: In this case-control study, 160 blood samples of participants including 80 patients with diabetic retinopathy and 80 healthy individual were tested. Genotyping of GPX-1 gene was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) by ApaI enzyme. Data analysis was performed using MedCalc (12.1) program.

Results: The genotype frequencies of the GPX-1 in DR patients for Leu/Leu, Leu/Pro, Pro/Pro were 10%, 62.5% and 27.5%, respectively, while for the control groups were 10%, 70% and 20%, respectively.In ohter words, Ile/Pro heterozygote was the most frequent genotype in patients and controls. According to the results of this study, there was not significant difference between patients with diabetic retinopathy and controls(p=0.52).

Conclusion: It is concluded that GPX-1 gene Pro 198 Leu polymorphism is not associated with DR. Further research is required to clarify the role of GPX-1 gene in DR in Rasht population along higher sample size.

Background: Hepatitis B virus (HBV) is a member of hepadenaviridae family, which is infectious for humans and a few animal species. Successful clearance and elimination of infection from the body or development of HBV infection to chronic disease depend on the host genetic background in immune system genes. Interleukin-12 (IL12) and also Interleukin-12 Receptor B1 (IL 12 RB1) are the key factors in the spontaneous clearance of viral infections, especially HBV. The aim of the present research is to investigate the association between Interleukin-12 receptor B1 gene polymorphism (rs11575934 A/G) and susceptibility to chronic Hepatitis B virus infection.

Materials and Methods: In this case-control study, genomic DNA of 150 chronic HBV infected patients and 150 healthy controls were extracted from peripheral blood cells. Single nucleotide polymorphism (rs11575934 A/G) was genotyped using polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP).

Results: The frequency of GG, AG, AA genotypes was 6.7%, 40.7%, and 52.7% in chronic patients and 12.7%, 41.3%, and 46% in control group, respectively. No statistically significant difference between case and control groups has been observed (p=0.176).

Conclusion: In the present study, no significant correlation between rs11575934 A/G single nucleotide polymorphism of the IL12RB1 gene and susceptibility to chronic hepatitis B virus infection has been observed. According to the study, this polymorphism does not affect the susceptibility to chronic HBV infection.

Background: Recurrent pregnancy loss (RPL) is a heterogeneous condition with the prevalence of more than 1% among women of reproductive age, which is defined as the occurrence of more than two miscarriages. Immune-mediators, cytokines, determine the role of immune cells in response to tissue incompatibility conditions. Colony stimulating factor 3 (CSF3) is a cytokine affecting the expression of other cytokines such as IL-4, and suppressing the immune response against semi-allograft embryo. This study was done for the first time on the association of the rs1042658 polymorphism at 3’UTR of the CSF3 gene with the susceptibility to recurrent pregnancy loss, supposing the effect of it on the expression level and stability of the CSF3 gene transcript.

Materials and Methods: 122 RPL women and 140 healthy fertile women as a control group were enrolled in this case-control study. Genotype distribution of the selected polymorphism was evaluated by T-ARMS PCR method and the results were analyzed by logistic regression test.

Results: comparison of the genotypic frequencies in the 3'UTR of the CSF3 gene in patients and controls resulted in the statistically significant difference in the incidence of pregnancy loss in order to the protection effect of the genotypes carrying T allele was observed between two groups (p<0.05). History of the abortion among the relatives of RPL women versus the relatives of controls showed significant differences (p=0.05).

Conclusion: Findings showed significant relationship between rs1042658 polymorphism and the risk of recurrent pregnancy loss, which can affect the susceptibility of the condition.

Background: ANKK1 (ankyrin repeat and kinase domain containing 1) gene is a member of the serine/threonine kinase family. This family involved in signal transduction pathways. This gene contains Taq1A (rs1800497) single nucleotide polymorphism. The A1 allele carriers of TaqIA polymorphism have shown reduced DRD2 (Dopamine Receptor D2) receptors. This decrease predisposes individuals to seek for addictive substances to compensate this deficiency in dopaminergic system. The present study investigated TaqIA (rs1800497) polymorphism in heroin and methamphetamine addiction.

Materials and Methods: In this case-control study, 91 male methadone-maintained heroin and methamphetamine addicts and 100 male healthy controls were studied. Genomic DNA extraction was carried out from peripheral blood through salting-out method and individuals were genotyped for TaqIA polymorphism by RFLP-PCR technique and TaqI enzyme was used for RFLP.

Results: This survey revealed the significantly higher frequency of the A1 allele of TaqIA polymorphism in patients than control individuals (p<0.001). The frequency of A1 allele in patient and control individuals was %51 and %22.5, respectively. The A1A1 genotype was detected in 25% of patients and 7% of controls (p<0.001, OR=9.7, 95% CI=3.64-25.85).

Conclusion: The results of this study revealed that the A1 allele of TaqIA polymorphism is significantly associated with heroin and methamphetamine addiction.

Background: Inflammatory bowel disease (IBD) includes two basic categories ulcerative colitis (UC) and Crohn's disease (CD) that the etiology of which remains unclear. Tumor necrosis factor alpha (TNFα) promoter polymorphisms are a good candidate for susceptibility to IBD as there is a significant relationship between them. The main aim of this study was to assess TNFα gene polymorphisms with IBD susceptibility at positions -1031in Iranian patients.

Materials and Methods: In this case-control study, were studied 101 patients with IBD (86 ulcerative colitis, 15 Crohn's disease) and 100 healthy controls were studied. PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) was used for determining of genotyping. In following, allele frequency and genotype distribution of polymorphism T> C in TNFα gene between the case and control groups were typed.

Results: The frequency of genotype TT, TC and CC among patients was 64.4%, 28.7% and 6.9% and in control group was 63%, 29% and 8%, respectively. Also, allele frequency T-1031 of TNFα gene in IBD patients was high, while there is no statistical significant(p>0.05).

Conclusion: There was no significant correlation between TNFα gene polymorphisms and susceptibility to IBD at position -1031. Our results showed that TNFα gene polymorphisms cannot be considered as a potential prognostic marker cause of IBD in Iranian population.

Background: Endometriosis disease is considered as a common disease dependent on androgen hormones. Androgens have different effects on endometrial growth. Androgen receptor as a signal transduction pathway could have a key role in regulating the process. Over hundreds of mutations leading to resistance gene function in androgen receptor (AR) has been recorded. Among these, the seuaence of CAG repeat in exon 1 had the largest share of studies related to the disease. The aim of the present study was to investigate the relationship between the AR gene CAG repeat variations in Iranian women with endometriosis.

Materials and Methods: In this study, 100 women with endometriosis and 100 healthy women as controls were selected. Exon 1 was amplified using PCR. Products of PCR were studied to determine CAG repeat variation in acrylamide gels.

Results: The number of CAG repeats in each group was determined between 18-26 repeats (mean±standard, 18.35±3.3).

Conclusion: According to the results of this study, no significant differences were found between the two groups of healthy women and women with endometriosis. The number of CAG repeats in each group was determined between 18-26 repeats which indicates a lack of relationship between CAG repeat diversity and endometriosis. According to the information, this study was conducted on patients with endometriosis in iran for the first time, although studies with larger sample are needed.

Background: Niemann-Pick disease (NPD) refers to a group of lysosomal storage diseases that causes abnormal metabolism of lipids. One of the genes that play a role in the pathogenesis of this disease is SMPD1. To date, more than hundred disease- causing mutations have been identified in SMPD1 gene. Due to the large number of mutations in this gene, direct analysis of the mutations is costly and time-consuming. Therefore, indirect linkage analysis using polymorphic markers as an alternative method for molecular diagnosis of the mutations has been recommended. In the present study, allele frequency of rs1542705 genetic marker was analyzed in the Iranian population. The aim was to determine the polymorphic information content (PIC) and the possibility of its application in indirect diagnosing of NPD.

Materials and Methods: After bioinformatics analysis of the SMPD1 gene region, rs1542705 marker was selected for genotyping in Isfahan population. In order to calculate the allele and genotype frequency of the marker, molecular tests were done on 113 DNA samples of unrelated healthy individuals by using ARMS-PCR technique. Finally, the information related to the genotype of the individuals was statistically analyzed using Powermarker and Genepop software.

Results: The analyses showed that the studied population was in accordance with Hardy-Weinberg equilibrium. Allele frequency of rs1542705 marker for T and C alleles was 71.24% and 28.76%, respectively, and the heterozygosity of the marker was 43.36%. Also, polymorphic information content (PIC) was 0.325.

Conclusion: The results of this study showed that rs1542705 marker could be considered as an informative marker for molecular diagnosis of Niemann- Pick disease using linkage analysis in the studied population.

Background: Breast cancer is both the prevailing malignancy and the most common cause of cancer death among women. Many factors may play a role in the susceptibility to the breast cancer and Oxygen Free Radicals may be one of these. There are various known antioxidant systems against oxidative stress, including ParaoxonaseI. The aim of this study was to investigate the association between rs854560 polymorphism in the PON1 gene in patients with breast cancer.

Materials and Methods: We performed genotyping analysis using polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) assay in a case–control study of 83 confirmed breast cancer patients and 100 cancer-free controls in Markazi Province.

Results: In our study of the PON1 gene L55M polymorphism, the LL genotype was found in 2 (2.40%) patients, whereas the LM genotype was found in 69 (83.13%) patients. The MM genotype was present in 12 (14.45%) patients. In the control group, LL, LM and MM genotypes were found in 4 (4%), 81 (81%), and 15 (15%) subjects, respectively. There was no statistically significant difference between patient and control groups in terms of the PON1 gene L55M polymorphism (p= 0.825). Allele distributions were different but this difference did not reach statistical significance (p= 0.920).

Conclusion: We found no association between M55L polymorphism and breast cancer.

Abstract

Background: Osteoporosis is describesd as a disorder and skeletal disease that decrease bone strength and increases the risk of a bone fractures. Genetic factors have effect role in the progression of the osteoporosis. The aim of this study was to investigate the association between LRP4 gene polymorphism with osteoporosis in a population of postmenopausal women from north of Iran.

Materials and Methods: In this case-control study, 80 female patients with osteoporosis and 80 healthy females without osteoporosis with average age of 45-60 has been investigated. After DNA extraction from genome samples, polymorphism of LRP4 (rs4752947) gene have been investigated by PCR-RFLP method. Data were analyzed by SPSS software.

Results: Our results showed no significant relationship between polymorphism of LRP4(rs4752947) gene and the risk of osteoporosis disease in two patients and control groups. Also, AT genotype and TT genotype compared with AA genotype increased the chance of disease by 1379 and 3.5, respectively. In addition, TT alleles compared with AA alleles, increased the chance of osteoporosis up to 1.605 times.

Conclusion: Of course, more complementary studies considering other LRP4 gene subtypes with more individuals for better findings are needed.

Abstract

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with broad clinical manifestations, but unclear etiology. Extensive tissue damage occurs due to the production of auto-antibody against nuclear and cytoplasmic antigens. Regarding the involvement of GADD45A gene in cell cycle control, T-cell proliferation suppression, and genome epigenetic regulation, this case-control study was done for the first time to evaluate the association of rs581000 polymorphism in 5’ near gene with the risk of SLE among patients in south of Iran.

Materials and Methods: This study was performed on 102 patients with SLE in comparison with 118 healthy controls. Genotyping of the GADD45A rs581000 polymorphism was performed using T-ARMS PCR.

Results: The T allele was significantly more frequent in the controls (0.13) than in the patients (0.01) with SLE (p<0.001). The frequency of genotypes carrying at least one C allele (CC+CG) was higher in control group (14.4%) compared to patient group (1%), and this allele showed protective effect against the risk of SLE (p<0.001, CI: 0.009-0.5, OR=0.06)

Conclusion: It seems that GADD45A rs581000 polymorphism involved in the SLE pathogenesis.

Abstract

Background: Polycystic ovary syndrome(PCOS) is the most common endocrine aberration in women. PCOS is characterized by ovarian hyperandrogenism and anovulation resulted from a disorder of follicular maturation. Apoptosis is a regulatory mechanism for oocyte maturation and survival. Several studies have shown a possible role of Fas in ovarian apoptosis. The present study is the first investigation to examine the possible association of Fas rs1800682gene polymorphism with PCOS risk in Iranian women.

Materials and Methods: This case-control study was conducted on 251 patients with PCOS and 213 healthy control women. The Fas rs1800682 gene polymorphism genotypes were analyzed using the Tetra-ARMS-PCR method. Also, logistic regression analysis was used to investigate the association between genotypes and PCOS risk.

Results: There was a significant association between A allele and susceptibility to PCOS(OR =1.4, %95CI=1.08-1.83, p=0.011). Moreover, in the recessive genetic model for A allele, the AA genotype increased the risk of PCOS after adjusting age and body mass index(OR=1.6, %95CI=1.02-2.51, p=0.041).

Conclusion: For the first time, this study showed that Fas rs1800682 polymorphism is associated with PCOS risk in Iranian women and the A allele may act as a recessive allele for increasing the risk of PCOS.

Background: Biological and epidemiological data indicate that the levels of vitamin D maybe affect the breast cancer risk. Vitamin D plays an important role in cell proliferation, apoptosis and tumor growth suppression. Vitamin D receptor is a critical mediator for the cellular reactions of vitamin D. Some of the epidemiological studies, reviewed the relationship between VDR gene polymorphism ApaI and breast cancer, but the controversial findings have been achieved.

Materials and Methods: In this study, a population-based case-control study including 140 patients and 160 healthy individuals of women in Markazi Province were evaluated using PCR-RFLP approach. Genomic DNA was extracted from blood samples using the salting-out procedure. Polymorphism of interest was determined by PCR-RFLP method using ApaI enzyme and statistical analysis was performed by SPSS software.

Results: Based on the results of this study, distribution of AA genotype in cancer and control groups was, 38.6 and 26.87, for AC genotype 55.00 and 66.87, and finally for CC genotype 6.43 and 6.26 respectively. The results of this study showed no association between ApaI polymorphism of the VDR gene and breast cancer(OR=0.903,CI=95%, 0.29-2.95.)

Conclusion: In this study, we found no association between ApaI polymorphism and breast cancer, which are consistent with the findings of some other researchs. It is necessary to examine a larger population to achieve more definitive results.