FOXP3 rs3761548 polymorphism is associated with knee osteoarthritis in a Turkish population.

AIM: Functional polymorphisms located in FOXP3 intron 1 was recently found to be associated with rheumatoid arthritis (RA). Although RA is an autoimmune disease, there is supporting evidence that activated maladaptive responses including pro-inflammatory pathways play roles in osteoarthritis (OA), similar to RA. The aim of this study was to explore the relationship between rs2232365 (-924A/G) and rs3761548 (-3279A/C) polymorphisms as well as possible changes in the 600 bp promoter region of FOXP3 and knee OA. METHODS: Patients with primary knee OA (n = 300) and healthy individuals (n = 300) were examined for rs3761548 and rs2232365 FOXP3 gene polymorphisms by the polymerase chain reaction-restriction fragment-length polymorphism method. The 600 bp promoter region (between -500 and +100) of the gene was also sequenced with direct sequencing in 50 knee OA patients and 50 healthy individuals. RESULTS: There were no sequence variants in the promoter region tested both in OA patients and healthy controls. The SNP rs2232365 showed no association with OA susceptibility and severity and the results of other genetic models were also nonsignificant. On the other hand, rs3761548 AC (P = 0.003), AA + CC (P = 0.0014) as well as AC + AA (P = 0.40) genotypes showed association with Grade 4 knee OA patients. CONCLUSION: Our findings indicated that the association between FOXP3 rs2232365 polymorphism and knee OA tended to yield negative results but the FOXP3 rs3761548 C allele was associated with elevated risk of OA in Grade 4 knee OA patients in a Turkish population.

Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population

Background: Breast cancer is a leading cause of death in women worldwide. Genetic polymorphisms have been reported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutations in p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphism on breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an association between MDM2 T309G (rs2279744) polymorphism and breast cancer in a Turkish population. Materials and Methods: We analysed 110 patients with breast cancer and 138 matched? controls. For genotyping, polymerase chain reaction and restriction length fragment polymorphism methods were used. Results: A significant difference was observed between case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). There was a significantly higher frequency of the TT genotype in the control group (p=0.028; OR, 2.42; 95% CI, 1.09-5.37). However, we did not find any relationships among tumor grade and metastasis status and this polymorphism. Conclusion: This study indicates that the MDM2 T309G polymorphism GG genotype and the TG+GG combination may be risk factors for breast cancer in our Turkish population.

Studying the Association between Sudden Hearing Loss and DNA N-Methyltransferase 1 (DNMT1) Genetic Polymorphism.

OBJECTIVE: The aim of the present study was to investigate whether there was any relationship between some DNA N-methyltransferase 1 (DNMT1) polymorphisms and susceptibility to idiopathic sudden sensorineural hearing loss (ISSHL) in ISSHL patients. MATERIAL AND METHODS: We investigated 90 patients diagnosed with ISSHL and a control group composed of 75 age- and gender-matched healthy individuals. DNA was extracted from the blood samples by phenol-chloroform method. Polymerase chain reaction and restriction fragment length polymorphism methods were used for the genotyping analysis of 4 regions of DNMT1. RESULTS: For rs2228612 single nucleotide polymorphism (SNP), the frequency of AA, AG, and GG genotypes were 81.4%, 9.3%, and 9.3% in controls and 82.2%, 16.7%, and 1.1% in patients, respectively. We observed a significant decrease in the frequency of GG genotype in patients with ISSHL when compared with controls (p=0.027). The frequency of GG, AG, and AA genotypes for rs2228611 SNP were 20.7%, 49.3%, and 20% in controls and 20%, 47.8%, and 32.2% in patients, respectively. There was a significantly increased frequency of the AA genotype of this SNP in the DNMT1 gene, and we found that individuals with the AA genotype had 2.47 times the risk for ISSHL development than individuals with the GG genotype (p=0.41). The GAA haplotype may constitute 2.66 times the risk for ISSHL disease (OR=2.66, 95% confidence interval: 0.28-25.03). CONCLUSION: This study's results showed that the AA genotype in rs2228611 polymorphism was a risk factor in ISSHL patients and the GG genotype could be a protective factor in rs2228612 polymorphism.

Significant Association Between Polymorphisms of Wnt Antagonist Genes and Lung Cancer.

Further elucidation of the molecular mechanisms underlying lung cancer (LC) is essential for the development of new effective therapeutic agents. Recently, involvement of Wnt antagonists in oncogenesis has been demonstrated in several cancers. The investigation of their contribution to lung carcinogenesis is still under investigation. We aimed to investigate whether there is a susceptibility or preventive effect of Wnt antagonist gene polymorphisms on the development and/or prognosis of LC. We investigated 110 LC patients and 160 controls. Single-nucleotide polymorphisms of Wnt antagonist genes including DKK2 (rs17037102), DKK3 (rs3206824), DKK3 intron4 G/C (rs7396187), DKK4 (rs2073664), and sFRP4 (rs1802074) were analyzed using nested polymerase chain reaction and restriction fragment length polymorphism. Results showed that patients with DKK3 AA compared with controls have a decreased risk of LC (adjusted for smoking habit, body mass index, and familial history) (P = 0.02; odds ratio [OR],0.08; 95% confidence interval [95% CI], 0.01-0.7). It was found that, for sFRP4 polymorphism, patients with GG and GA genotypes versus AA genotype controls showed a decreased risk for LC (P = 0.01; [OR, 0.19; 95% CI, 0.05-0.73 for GG genotype]; [OR = 0.18, 95% CI, 0.04-0.72 for GA genotype]). In addition, a decreased risk of LC was also found for the genotype combination of DKK3 (rs3206824) GG and sFRP4 AG + GG (P = 0.004; OR, 0.12; 95% CI, 0.02-0.58). We suggest that these 2 polymorphisms have a protective effect on LC in this study.

AXIN2 polymorphism and its association with prostate cancer in a Turkish population.

Polymorphism of AXIN2, a component of Wnt signaling, has been shown to play a role in tumorigenesis and dysregulated in cancer cells. In order to find out if AXIN2 polymorphism is a risk factor for prostate cancer, we analyzed eight polymorphic regions of this gene in 84 patients with prostate cancer and compared the results with 100 healthy controls in a Turkish population using PCR-RFLP methods. The genotype frequencies and risk factors of prostate cancer and control groups were analyzed by Chi-square test. We found a statistically significant result between prostate cancer risk and AXIN2 Intron2-956+16A/G (rs35285779) SNP. The frequency of the homozygous G/G (0%) and heterozygous A/G (18%) genotypes was significantly less in patients with prostate cancer than in healthy controls (7 and 32%, respectively) (P<0.05) for this SNP. When compared with the wild-type A/A genotype of the controls, prostate cancer patients with the A/G and G/G genotype showed reduced risk of cancer; the adjusted odds ratio (OR) for patients with the homozygous G/G genotype was 0.87 (95% CI: 0.81-0.95) and for heterozygous A/G genotype was 0.42 (95% CI: 0.20-0.85). We found no statistically significant association between controls and prostate cancer for other seven SNPs of AXIN2 including Exon1-148 C/T (rs2240308), Exon1-432 T/C (rs2240308), Exon5-1365 G/A (rs9915936), Exon5-1386 C/T (rs1133683), Intron5-1712+19 T/G, Exon7-2062 C/T, and Intron7-2141+73 G/A (rs4072245) (P>0.05). These results suggest that the AXIN2 Intron2 rs35285779 SNP is associated with development of prostate cancer as a protective SNP, while an association between other seven SNPs of the AXIN2 and risk of prostate cancer was not observed.