Maryam Rezaei

Effect of TP53 16-bp and β-TrCP 9-bp INS/DEL polymorphisms in relation to risk of breast cancer.

UNLABELLED P53 as a tumor suppressor and an apoptosis modulator, is the regulator of the cell cycle and apoptosis, and contributes to mammary gland development and breast cancer (BC) progression. BTRC gene (Homo sapiens beta-transducing repeat containing E3 ubiquitin protein ligase) encoded protein, β-TrCP, is a novel regulator of p53. The current study aimed to assess the possible effects of TP53 IVS3 16 bp (rs17878362) and β-TrCP 9 bp (rs16405) INS/DEL polymorphisms on BC risk in an Iranian population. A total of 439 women including 236 BC patients and 203 healthy women were recruited. The TP53 and β-TrCP INS/DEL polymorphisms were genotyped by allele-specific polymerase chain reaction method. Our data demonstrated that the TP53 16-bp INS/DEL variation was associated with an increased risk of BC in codominant (INS/INS vs. DEL/DEL OR=1.82; 95% CI=1.02-3.23; P=0.042) and dominant (Del/INS+INS/INS vs. DEL/DEL OR=1.48; 95% CI=1.03-2.21; P=0.044) models. Additionally, the variant allele (INS) of TP53 DEL/INS polymorphism with a relatively higher frequency in cases than in controls (35.6 vs. 27.8) was a risk factor for BC (OR=1.43; 95% CI=1.06-1.93; P=0.017). With respect to β-TrCP INS/DEL polymorphism, our study failed to find any difference in allele and genotype distribution between BC patients and controls in codominant, dominant and recessive tested inheritance models (P>0.05). Furthermore, no significant association among the β-TrCP and TP53 genotype distribution and clinical characteristics of BC patients were found (P>0.05). Our findings suggest that the TP53 16-bp INS/INS and DEL/INS+INS/INS genotypes as well as the INS allele could be genetic factors related to BC risk.

Association between polymorphisms in TP53 and MDM2 genes and susceptibility to prostate cancer

Tumor protein 53 (TP53), a tumor suppressor gene, is a vital cellular cancer suppressor in multicellular organisms. Murine double minute-2 (MDM2) is an oncoprotein that inhibits TP53 activity. A number of studies have examined the association of TP53 and MDM2 polymorphisms with the risk of common forms of cancer, but the findings remain inconclusive. The present study aimed to evaluate the impact of the 40-bp insertion/deletion (I/D) polymorphism (rs3730485) in the MDM2 promoter region and the 16-bp I/D polymorphism (rs17878362) in TP53 on the susceptibility of prostate cancer (PCa) in a sample of the Iranian population. This case-control study included 103 patients with pathologically confirmed PCa and 142 patients with benign prostatic hyperplasia. The MDM2 40-bp I/D and TP53 16-bp I/D polymorphism was determined using polymerase chain reaction analysis. The results demonstrated that the MDM2 40-bp I/D polymorphism increased the risk of PCa in a co-dominant inheritance model [odds ratio (OR)=1.88; 95% confidence interval (CI)=1.11-3.19; P=0.023, D/D vs. I/I], while this variant marginally increased the risk of PCa in a dominant model (OR=1.69; 95% CI=1.00-2.83; P=0.051, I/D+D/D vs. I/I). No significant association was observed between the TP53 16-bp I/D polymorphism and PCa. In conclusion, the present study demonstrated that the 40-bp I/D polymorphism in the MDM2 promoter increased the risk of PCa in an Iranian population. Further investigations with diverse ethnicities and larger sample sizes are required to verify these results.

Association Between Vascular Endothelial Growth Factor Gene Polymorphisms with Breast Cancer Risk in an Iranian Population.

Breast cancer (BC) is one of the most causes of death in women worldwide. It affects Iranian female population approximately a decade earlier than those in other parts of the world. Previous studies have shown that vascular endothelial growth factor (VEGF) gene variants were associated with BC risk. The current study aimed to evaluate the impact of VEGF rs3025039 (+936C>T), rs2010963 (+405C>G), rs833061 (–460T>C), rs699947 (–2578C>A), and rs35569394 (18-bp I/D) polymorphisms on BC risk in an Iranian population in southeast of Iran. This case-control study was done on 250 BC patients and 215 healthy women. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or PCR was used to genotype the polymorphisms. Our findings showed that VEGF rs699947 variant increased the risk of BC (OR = 1.71, 95% CI = 1.15–2.54, P = 0.009, CA vs CC; OR = 2.12, 95% CI = 1.14–3.93, P = 0.021, AA vs CC; OR = 1.78, 95% CI = 1.22–2.60, P = 0.004, CA+AA vs CC; OR = 1.47, 95% CI = 1.12–1.92, P = 0.005, A vs C). The VEGF rs3025039, rs2010963, rs833061, and rs35569394 variants were not associated with risk/protection of BC. In conclusion, our results proposed that VEGF rs699947 polymorphism may increase the risk of BC development. Furthers studies with larger sample sizes and different ethnicities are necessary to confirm our findings.

Evaluation of HLA-G 14 bp Ins/Del and +3142G>C Polymorphism with Susceptibility and Early Disease Activity in Rheumatoid Arthritis.

Purpose/Background. Mounting evidence designates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. There are controversial reports concerning the impact of HLA-G gene polymorphism on rheumatoid arthritis (RA). This study was aimed at examining the impact of 14 bp ins/del and +3142G>C polymorphism with susceptibility and early disease activity in RA patients in a sample of the Iranian population. Methods. This case-control study was done on 194 patients with RA and 158 healthy subjects. The HLA-G rs1063320 (+3142G>C) and rs66554220 (14 bp ins/del) variants were genotype by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP) and PCR method, respectively. Results. The HLA-G +3142G>C polymorphism significantly decreased the risk of RA in codominant (OR = 0.61, 95% CI = 0.38–0.97, p = 0.038, GC versus GG; OR = 0.36, 95% CI = 0.14–0.92, p = 0.034, CC versus GG), dominant (OR = 0.56, 95% CI = 0.36–0.87, p = 0.011, GC + CC versus GG), and allele (OR = 0.58, 95% CI = 0.41–0.84, p = 0.004, C versus G) inheritance models tested. Our finding did not support an association between HLA-G 14 bp ins/del variant and risk/protection of RA. In addition, no significant association was found between the polymorphism and early disease activity. Conclusion. In summary, our results showed that HLA-G +3142G>C gene polymorphism significantly decreased the risk of RA in a sample of the Iranian population.

Association of Genetic Polymorphisms of IFNGR1 with the Risk of Pulmonary Tuberculosis in Zahedan, Southeast Iran

Aim. The present study was undertaken to find out the possible association between interferon-gamma (IFN-γ) receptor 1 (IFNGR1) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Methods. Polymorphisms of IFNGR1 rs1327474 (−611 A/G), rs11914 (+189 T/G), rs7749390 (+95 C/T), and rs137854905 (27-bp ins/del) were determined in 173 PTB patients and 164 healthy subjects. Results. Our findings showed that rs11914 TG genotypes decreased the risk of PTB in comparison with TT (OR = 0.36, 95% CI = 0.21–0.62, and p = 0.0002). The rs11914 G allele decreased the risk of PTB compared with T allele (OR = 0.41, 95% CI = 0.25–0.68, and p = 0.0006). IFNGR1 rs7749390 CT genotype decreased the risk of PTB in comparison with CC genotype (OR = 0.55, 95% CI = 0.32–0.95, and p = 0.038). No significant association was found between IFNGR1 rs1327474 A/G polymorphism and risk/protective of PTB. The rs137854905 (27-bp I/D) variant was not polymorphic in our population. Conclusion. Our findings showed that IFNGR1 rs11914 and rs7749390 variants decreased the risk of PTB susceptibility in our population.

Association between LAPTM4B gene polymorphism and prostate cancer susceptibility in an Iranian population

ABSTRACT Lysosome associated protein transmembrane 4 β (LAPTM4B) is an oncogene associated with many human cancers. In the present study we aimed to examine the possible association between LAPTM4B polymorphism and risk of prostate cancer (PCa) in an Iranian population. This case control study was performed on 168 patients with PCa and 176 controls with benign prostatic hyperplasia (BPH). Genomic DNA was extracted from whole blood and LAPTM4B genotypes were identified by polymerase chain reaction. The distributions of LAPTM4B genotypes were significantly different between PCa patients (60.7% for *1/1, 32.8% for *1/2, and 6.5% for *2/2) and controls (44.9% for *1/1, 49.4% for *1/2, and 5.7% for *2/2). Both the *1/2 and *1/2+*2/2 genotypes significantly decreased the risk of PCa compared with the *1/1 genotype (OR = 49, 95% CI = 0.31–0.77, p = 0.002 and OR = 0.53, 95% CI = 0.34–0.81, p = 0.004, respectively). The minor allele (LAPTM4B*2) was associated with a decreased risk of PCa compared with the LAPTM4B*1 allele (OR = 0.68, 95% CI = 0.48–0.96, p = 0.031). Moreover, LAPTM4B polymorphism was not associated with clinicopathological characteristics of PCa patients. The results of this study showed that LAPTM4B*2 was associated with a decreased risk of PCa but the clinicopathological characteristics of PCa were not linked to LAPTM4B polymorphism. Further studies with larger sample sizes and different ethnicities are needed to confirm our findings.

Evaluation of prodynorphin gene polymorphisms and their association with heroin addiction in a sample of the southeast Iranian population

Genetic factors are supposed to account for about 30-50% of the predisposition to cocaine and heroin addiction. This study aims at investigating the effect of rs2281285, rs2235749, rs910080 and 68bp VNTR polymorphisms of prodynorphin (PDYN) gene on heroin dependence risk in a sample of the southeast Iranian population. This case-control study was done on 216 heroin dependence subjects and 219 healthy subjects. Genomic DNA was extracted from peripheral blood cells using salting out method. Genotyping of PDYN polymorphisms were performed using polymerase chain reaction (PCR) or PCR-RFLP method. The findings showed that PDYN rs910080 T>C variant significantly increased the risk of heroin dependence (OR=7.91, 95%CI=3.36-18.61, P<0.0001, CC vs TT; OR=7.53, 95%CI=3.30-17.16, P<0.0001, CC vs TT+TC; OR=1.75, 95%CI=1.33-2.32, p<0.0001, C vs T). The rs2235749 C>T, rs2281285 A>G and 68bp VNTR variants of PDYN gene were not associated with heroin dependence. Altogether, our results provide an association between rs910080 polymorphism of PDYN gene and risk of heroin dependence in a sample of the southeast Iranian population.

Association study of the FTO gene polymorphisms with the risk of pulmonary tuberculosis in a sample of Iranian population

AIM The aim of the present study was to find out the impact of fat mass and obesity-associated (FTO) gene on risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. METHODS This case-control study was carried out on a total of 354 subjects including 185 PTB patients and 169 healthy subjects. Genotyping of FTO rs9939609 and rs8050136 variants was done using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS FTO rs9939609 variant showed no statistically significant difference in allele and genotype frequencies between PTB patients and controls. The rs8050136 polymorphism marginally increased the risk of PTB in dominant (OR = 1.53, 95% CI = 1.00-2.33, p = 0.055, CA+AA vs. CC) inheritance model tested, where rs8050136 A allele significantly increased the risk of PTB (OR = 1.42, 95% CI = 1.02-1.97, p = 0.045) compared with C allele. CONCLUSION The finding of the present study showed an association between FTO rs9939609 variant and risk of PTB. Further studies with larger sample sizes and different ethnicities are necessary to confirm the findings.

Association of Endothelin-1 rs5370 G>T gene polymorphism with the risk of nephrotic syndrome in children

Background: Primary nephrotic syndrome (NS) is a common kidney disease in children. Objectives: The present study was aimed to investigate whether rs5370 G>T (lys198Asn) genetic variant of endothelin-1 (ET-1) is involved in the susceptibility to NS. Patients and Methods: This case-control study was performed on 138 patients with NS and 150 healthy children. Genomic DNA was extracted from whole blood using salting out method. Polymorphism of the ET-1 rs5370 G>T (lys198Asn) polymorphism detected by T-ARMS-PCR as well as PCR-RFLP method. Results: The results showed that the genotype and allelic frequencies of the ET-1 rs5370 G>T variant were not significantly different between cases and controls. Furthermore, subgroup analysis showed that rs5370 G>T variant was not associated with gender of patients. In NS patients the genotype was not associated with cholesterol, triglyceride, total protein and albumin levels. Conclusions: In conclusion, our findings indicate that ET-1 rs5370 G>T is not associated with NS. Further studies with larger sample sizes and different ethnicities are required to validate our findings.