Gokhan Bagci

The Role of the CCR2 Gene Polymorphism in Abdominal Aortic Aneurysms

Objective: Chronic inflammation play an important role on abdominal aortic aneurysms (AAA) formation. Chemokine receptor-2 (CCR2) is involved in regulation of the inflammatory response. However, relation between CCR2 polymorphism and AAA formation in human has not yet been investigated. In this study, we aimed to investigate the relationship between AAA and CCR2-V64I gene polymorphism. Methods: In this study, 100 consecutive patients with AAA and 138 individuals with normal aortic diameter were included. CCR2-V64I gene polymorphism were analyzed by PCR-RFLP technique. Genotype distribution and allele frequencies of CCR2-V64I gene polymorphism in patients with AAA and healthy subjects were compared. Results: CCR2 heterozygote V64I polymorphism and allele frequency were more frequently observed in the AAA group (p = 0.01, p = 0.004). Significant relationship was observed between CCR2 V64I polymorphism (OR:2.31, 95% CI:1.19-4.46, p = 0.01) and presence of AAA in multivariate regression analysis. Conclusion: The present study, showed us a relationship between CCR2-V64I polymorphism and AAA.

Renalase gene polymorphism is associated with increased blood pressure in preeclampsia

BACKGROUND Renalase is a novel enzyme that degrades circulating catecholamines. We aimed to investigate the role of rs2576178 and rs10887800 polymorphisms of the renalase gene in preeclampsia (PE) patients METHODS This case-control study consisted of 110 women with PE and 102 normotensive controls. PCR-RFLP method was used for determination of renalase gene polymorphisms. RESULTS Allele frequency and genotype distribution of rs10887800 polymorphism were found statistically significantly higher in women with PE (p<0.05). Also G allele and GG genotype of rs10887800 polymorphism were found higher in women with severe PE than that of mild PE (p<0.05). There was no significant difference for rs2576178 polymorphism in terms of allele frequency and genotype distribution (p>0.05). In PE patients, systolic blood pressure (SBP) means according to rs10887800 genotypes were found statistically significantly higher (GG vs AA; p=0.001) and (GG vs GA; p=0.001). Similarly, diastolic blood pressure (DBP) means were found statistically significantly higher in PE patients (GG vs GA: p=0.001); (GG vs AA: p=0.004). For rs2576178 polymorphism, SBP means were found as (GG vs AA; p=0.012, GG vs GA; p>0.05) in PE patients. DBP means were not significant according to rs2576178 genotypes in PE patients (p>0.05). CONCLUSIONS The findings of the present study suggest that blood pressure may be increased by GG genotype and G allele of rs10887800 polymorphism and the polymorphism may increase the susceptibility to PE.

KRAS, BRAF oncogene mutations and tissue specific promoter hypermethylation of tumor suppressor SFRP2, DAPK1, MGMT, HIC1 and p16 genes in colorectal cancer patients.

BACKGROUND Colorectal cancer is a serious disease that causes significant morbidity and mortality in developed countries. Genetic changes, such as mutations in proto-oncogenes and DNA repair genes, and loss of function in the tumor suppressor genes cause colorectal cancer development. Abnormal DNA methylation is also known to play a crucial role in colorectal carcinogenesis. OBJECTIVE In this study, frequencies of KRAS and BRAF mutations, promoter hypermethylation profiles of SFRP2, DAPK1, MGMT, HIC1 and p16 genes, and possible associations between hypermethylation of these genes and KRAS and BRAF mutations were aimed to find out. METHODS Ninety three colorectal cancer tissues and 14 normal colon mucosas were included in the study. Common twelve KRAS gene mutation were investigated with using reverse-hybridization strip assay method. BRAF V600E mutations were investigated with RFLP method. Hypermethylation status of five tumor suppressor genes were detected by using reverse-hybridization strip assay method after bisulfite modification of DNA. RESULTS KRAS and BRAF mutation frequencies were determined as 54.84% and 12.9%, respectively. Promoter hypermethylation frequencies of tumor suppressor genes SFRP2, DAPK1, MGMT, HIC1 and p16 were determined as 66.7%, 45.2%, 40.9%, 40.9% and 15.1%, respectively. Statistically significant associations were found between BRAF mutation and SFRP2 and p16 tumor suppressor genes hypermethylation (SFRP2; p= 0.005, p16; p= 0.016). Compared to rectum, SFRP2 (p= 0.017) and MGMT (p= 0.013) genes have statistically significantly higher promoter hypermethylation in colon. CONCLUSIONS Results of the current study have confirmed that KRAS mutations and SFRP2 hypermethylation can be used as genetic markers in colorectal cancer.

Relationship between IFNA1, IFNA5, IFNA10, and IFNA17 gene polymorphisms and Crimean-Congo hemorrhagic fever prognosis in a Turkish population range.

Crimean‐Congo hemorrhagic fever (CCHF) is a fatal emerging acute viral infection. Not much is known regarding the pathogenic mechanisms and the reasons behind severe or mild disease courses in CCHF. IFN‐alpha (IFNA) is one of the essential cytokines in the immune system. Existence of single nucleotide gene polymorphisms (SNPs) in cytokines can cause susceptibility or resistance to viral agents and different clinical courses. Hence, the relationship between SNPs in genes encoding cytokines (IFNA1 ‐1823G/A (rs1332190), IFNA5 ‐2529T/A (rs758236), IFNA10 Cys20stop (rs10119910), and IFNA17 Ile184Arg (rs9298814) SNPs and disease susceptibility were investigated. The associations between SNPs and CCHF prognosis were also studied. Total 150 patients with CCHF and 170 healthy individuals were enrolled. Genotyping was performed by PCR‐RFLP methods. The frequency of IFNA1 ‐1823 (rs1332190) GG genotype was significantly higher in control subjects than CCHF patients (20% vs. 8%; P = 0.01). For IFNA17 Ile184Arg (rs9298814) polymorphism, CCHF patients having TG genotype had a higher frequency than the control subjects (38% vs. 32.4%; P = 0.039). The distribution of TT + TG genotype frequencies was also significantly higher in CCHF group than the controls (97.3% vs. 91.8%; P = 0.049). Genotype and allele frequencies for IFNA subtypes between fatal and survivors were the same (P > 0.05). Genotype and allele frequencies between severe and mild/moderate CCHF patients were also the same (P > 0.05). The results show that IFNA1 rs1332190 and IFNA17 rs9298814 SNPs may play an important role in CCHF susceptibility. Determining the existence of other connections for IFNA SNPs and CCHF severity and fatality requires further investigations. J. Med. Virol. 88:1159–1167, 2016.

SDF-1/CXCL12 and CXCR4 gene variants, and elevated serum SDF-1 levels are associated with preeclampsia

ABSTRACT Objective: We aimed to compare the frequencies of stromal cell-derived factor-1 (SDF-1) 3′A and CXCR4 single-nucleotide polymorphisms (SNPs) and serum SDF-1 levels in patients with preeclampsia (PE). Methods: In total, 89 women with PE and 89 control women were included in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. Enzyme-linked immunosorbent assay method was used to measure serum SDF-1 level. Results: For SDF-1 3′A SNP, the frequency of GA genotype, total number of GA and AA genotypes, and the A allele frequency was higher in PE patients than controls (p = 0.04, 0.023, and 0.029, respectively). For CXCR4 SNP, the frequency of CT genotype, total number of CT and TT genotypes, and the T allele frequency were higher in PE patients than controls (p = 0.04, 0.006, and 0.005, respectively). SDF-1 serum level was detected higher in preeclamptic women compared with controls (p = 0.001). In PE patients, there was no significant association between serum SDF-1 levels and genotypes of SDF-1 3′A SNP. SDF-1 level was significantly higher in patients bearing CXCR4 CT genotype than CC genotype (p = 0.001). Furthermore, SDF-1 levels in patients bearing CT+TT genotype were found higher than that of patients with CC genotypes (p = 0.001). Conclusion: Results of our study suggest that SDF-1 3′A and CXCR4 polymorphisms and elevated serum SDF-1 levels may have a role in the development of PE.

Angiotensin-Converting Enzyme (ACE) I/D and Alpha-Adducin (ADD1) G460W Gene Polymorphisms in Turkish Patients with Severe Chronic Tinnitus.

OBJECTIVE Tinnitus is described as a disturbing sound sensation in the absence of external stimulation. We aimed to investigate whether there is any relationship between severe chronic tinnitus and angiotensin-converting enzyme (ACE) I/D and α-adducin (ADD1) G460W gene polymorphisms. MATERIALS AND METHODS The patient group and control group consisted of 89 and 104 individuals, respectively. The evaluation of tinnitus was performed using the Strukturiertes Tinnitus-Interview (STI). The Tinnitus Handicap Inventory (THI) was used to evaluate the tinnitus severity. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used for genotyping. RESULTS With regard to the ACE I/D polymorphism, there was no significant difference in genotype and allele frequencies between the patient group and control group. However, a statistically significant difference was found in genotype (p<0.01) and allele frequencies (p=0.021) of the ADD1 G460W gene polymorphism. Combined genotype analysis showed that the ACE II /ADD1 GW genotype was statistically significantly higher in the patient group than in the control group (X2: 7.15, p=0.007). The odds ratio value of the GW genotype was 2.5 (95% CI=1.4-4.7) (p<0.01). CONCLUSION Our results demonstrate an association between ADD1 G460W gene polymorphism and susceptibility to severe chronic tinnitus. It was found that the GW genotype increased the disease risk by 2.5-fold compared with other genotypes. This indicates that ADD1 G460W polymorphism could be an important factor in the pathophysiology of tinnitus.

Association of vitamin D receptor gene TaqI, FokI and ApaI variants with arteriovenous fistula failure in hemodialysis patients:

Purpose: We investigated the influence of the vitamin D receptor gene TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) polymorphisms in arteriovenous fistula failure in hemodialysis patients. Methods: This study was carried out with 54 patients who experienced two or more fistula failures in the late period after arteriovenous fistula operation and 58 control patients with no history of arteriovenous fistula failure in 3 years or longer. The polymerase chain reaction–restriction fragment length polymorphism method was used to determine the vitamin D receptor TaqI, FokI, and ApaI polymorphisms. Results: For vitamin D receptor gene TaqI and Fok1 polymorphisms, no significant association was found between the two groups (p > 0.05). However, a statistically significant association was determined for ApaI polymorphism between the two groups (p = 0.02). In patients, ApaI AA, AC, and CC genotype frequencies were found as 21 (38.9%), 32 (59.3%), and 1 (1.8%), respectively. However, genotype frequencies of AA, AC, and CC in the control group were 29 (50%), 22 (37.9%), and 7 (12.1%), respectively. In all three polymorphisms, no significant difference was found between the two groups in terms of allele frequencies (p > 0.05). Conclusion: Vitamin D receptor ApaI AC genotype may be a possible cardiovascular risk factor for the development of arteriovenous fistula failure.

Genetic variants in the microRNA machinery gene (Dicer) have a prognostic value in the management of endometrial cancer

Aim: Although several associations were found between Dicer rs3742330 single nucleotide polymorphism (SNP) and development and prognosis of some epithelial cancers, relationship between the SNP rs3742330 and endometrial cancer (EC) has not yet been studied. We aimed to investigate the prognostic role of rs3742330 SNP of Dicer gene in EC patients. Subjects and Methods: A total of 80 EC patients and 80 control subjects included in the study. Real-time polymerase chain reaction and the allele discrimination technique was used for genotyping of rs3742330 SNP. Results: There was no significant difference between EC patients and control subjects with regard to the genotype and allele frequencies for Dicer rs3742330 SNP (P > 0.05). Despite Dicer rs3742330 SNP had no prognostic value in terms of stage, grade, lymphovascular invasion, myometrial invasion, tumor size, and histopathology; malignant peritoneal cytology has been detected higher in the patients bearing AA genotype compare with AG genotype (P = 0.023). Higher recurrence rate and shorter time to recurrence were found in patients bearing AG and GG genotype compare with AA genotype (P = 0.009). Conclusion: Dicer rs3742330 AG and GG genotypes may have the potential to be used as a predictor of poor prognosis in the management of EC case.