Mavi Deniz Ozel

Association of Nicotinamide-N-Methyltransferase Gene rs694539 Variant with Patients with Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of a history of alcohol use and with a prevalence of 15%-45% in developed nations. Nonalcoholic steatohepatitis (NASH) is an advanced stage of NAFLD with a pronounced major inflammatory component. The aim of this study was to investigate the possible role of nicotinamide-N-methyltransferase (NNMT) gene rs694539 variant in the development of NASH. Therefore, we analyzed 80 NASH patients and 183 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism method developed in our laboratory. The NNMT rs694539 variant was found to be significantly associated with NASH (χ(2)=9.349, p=0.009). The individuals with the GG genotype had protection against NASH (χ(2)=3.793, p=0.051, odds ratio [OR]=0.580, 95% confidence interval [CI]=0.334-1.006), whereas the individuals with the AA genotype showed statistically significant increased risk for NASH (χ(2)=7.748, p=0.005, OR=7.338, 95% CI=1.448-37.190). Moreover, the G allele was protective against NASH (χ(2)=7.748, p=0.005, OR=0.136, and 95% CI=0.027-0.691). On the other hand, the A allele was a risk factor for NASH (χ(2)=3.793, p=0.051, OR=1.725, and 95% CI=0.994-2.996). Consequently, the rs694539 variant of NNMT gene is a genetic risk factor for developing NASH.

Association of nicotinamide-N-methyltransferase (NNMT) gene rs694539 variant with bipolar disorder

Here we report the association of the rs694539 variant of nicotinamide-N-methyltransferase gene with bipolar disorder in a case-control study of 95 bipolar disorder patients and 201 healthy controls (χ(2)=13.382, P=0.001). With the polymerase chain reaction restriction fragment length polymorphism method we developed we were able to show the association for the first time. This new finding may provide evidence to understand the mechanism of the disease.

ZNF804A rs1344706 Variant and Schizophrenia in a Romanian Population from Cluj Napoca

The ZNF804A rs1344706 variant was the first risk factor to be identified through genome-wide association studies and follow-up studies with meta-analysis for schizophrenia as well as bipolar disorders; we investigated 231 schizophrenia and 222 controls to see whether this particular variant was associated with schizophrenia in a Romanian population from Cluj Napoca. Clearly, there was no association between the ZNF804A rs1344706 variant and schizophrenia. Our study provides evidence for those that found no association with schizophrenia. A surprising result of our study was that the T allele frequency is the highest, thus far among the ethnic groups studied. We used a PCR-RFLP method that had been recently developed in our laboratory to the genotype ZNF804A rs1344706 variant. In conclusion, the ZNF804A rs1344706 variant was not associated with schizophrenia in the Romanian population from Cluj Napoca (χ(2)=0.734, p=0.693).

Gender-Specific Association of Methylenetetrahydrofolate Reductase Gene Polymorphisms with Sporadic Amyotrophic Lateral Sclerosis

Studies have revealed that elevated homocysteine levels can cause damage to motor neurons through multiple neurotoxic mechanisms, thus leading to the pathogenesis of amyotrophic lateral sclerosis (ALS). One way by which homocysteine levels are increased in the body is the consequence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. Therefore, to address this question, we studied the MTHFR C677T and A1298C polymorphisms in 437 sporadic ALS (SALS) and 439 healthy controls to learn whether they were associated with SALS. The overall SALS were not associated with MTHFR C677T and A1298C polymorphisms (χ(2)=1.378; p=0.502; χ(2)=1.304; p=0.521, respectively). However, when we stratified results in terms of gender, we found that the MTHFR C677T polymorphism (χ(2)=6.376; p=0.041), T677T genotype (χ(2)=5.508; p=0.019; odds ratio [OR]=2.561; 95% confidence interval [CI]=1.142-5.744), C677C/A1298A (χ(2)=5.216; p=0.022; OR=0.424, 95% CI=0.199-0.900), and T677T/A1298A (χ(2)=6.639; p=0.010; OR=2.900; 95% CI=1.252-6.717) compound genotypes were associated with SALS in female patients only. Moreover, stratification of SALS according to the onset of disease indicated that there was no association between MTHFR C677T (χ(2)=1.565; p=0.457; A1298C χ(2)=3.461; p=0.177) polymorphisms and overall spinal onset SALS. Further stratification analysis according to gender revealed that there was a remarkable association between MTHFR C677T (χ(2)=9.728, p=0.008), T677T genotype (χ(2)=7.820; p=0.005; OR=3.126; 95% CI=1.361-7.178) and T allele (χ(2)=5.000; p=0.025; OR=1.711; 95% CI=1.067-2.745), and T677T/A1298A compound genotype (χ(2)=9.108; p=0.003; OR=3.540; 95% CI=1.494-8.387) and spinal onset female SALS only. Likewise, there was also association between MTHFR A1298C polymorphism (χ(2)=5.946; p=0.051) and the C1298C genotype (χ(2)=5.282; p=0.022; OR=2.524; 95% CI=1.125-5.658), and the C677T/C1298C compound genotype (χ(2)=7.155; p=0.007; OR=1.045; 95% CI=0.983-1.112) and bulbar onset SALS only in women. In conclusion, the evidence we provide here clearly shows that MTHFR C677T and A1298C polymorphisms are genetic risk factors for SALS in women in a gender-specific manner whether they are of spinal or bulbar onset.

A Polymerase Chain Reaction–Restriction Fragment Length Polymorphism Method for Screening ZNF804A Gene Polymorphism (rs1344706) in Patients with Schizophrenia: A Significant Association

The original ZNF804A rs1344706 risk variant was identified through genome-wide association studies as a risk factor for schizophrenia. Follow-up studies involving meta-analysis have confirmed that rs1344706 is a risk factor for schizophrenia as well as bipolar disorders. We describe here a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to genotype ZNF804A rs1344706 variant in patients with schizophrenia. We generated a 220 bp fragment through PCR and subsequently cleaved it by the restriction endonuclease BsaBI, creating two fragments of 114 and 106 bp. Upon change in the nucleotide from T to G, the 106 bp fragment is further cleaved by BsaBI, thus creating two fragments of 87 and 19 bp. As a result, when the 220 bp fragment is cleaved by BsaBI restriction endonuclease, the TT genotype yields two fragments of 114 and 106 bp, and TG genotype four fragments of 114, 106, 87, and 19 bp, and the GG genotype three fragments of 114, 87, and 19 bp. Thus, this is a simple, fast, and cost-effective method to genotype the ZNF804A rs1344706 risk variant. Using this method, we were able to replicate an association between ZNF804A rs1344706 variant and schizophrenia in a Turkish population. Stratification analysis of the population according to the gender showed an association that was statistically significant among overall schizophrenia and male schizophrenia and the risk T allele and TT genotype of the ZNF804A gene.

TP53 Arg72Pro polymorphism in Turkish patients with sporadic amyotrophic lateral sclerosis

Recently, Eve et al. (2007) reported that the expression of TP53 (NM_000546) was increased by 2.1-fold in whole spinal cord and 2.7-fold in the ventral horn of amyotrophic lateral sclerosis (ALS) patients. Based on this particular observation, we decided to evaluate whether the TP53 Arg72Pro polymorphism (rs1042522) (C215G) was implicated in the etiopathology of sporadic amyotrophic lateral sclerosis (SALS). Therefore, we genotyped 394 Turkish SALS patients and 439 matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We did not find any association between overall SALS patients with the TP53 Arg72Pro polymorphism and controls (χ(2) = 2.674; p = 0.263). Consequently the TP53 Arg72Pro polymorphism was not associated with SALS.

EPA-0819 - Association of csfr2a gene rs4129148 and il3ra gene rs6603272 variants with schizophrenia

Introduction Schizophrenia is a devistating disorder which has a genetic component. Recently three reports showed that the IL3 gene, CSF2RA gene are associated with schizophrenia. Aims The objective of the study was to show whether there was an association between the IL3R gene rs6603272 variant and the CSF2RA rs4129148 variants with schizophrenia. Methods There was 264 schizophrenia patients and 222 controls from Romania. We utilized a PCR-RFLP method to genotype the subjects. Results The genotype frequencies of the IL3RA rs6603272 variant were TT, 54.2; TG, 39.8; and GG,6.1 % in cases and TT, 52.7; TG, 41.9; and GG,5.4 % in controls. The T allele frequency in both controls and cases was 74%. The genotype frequencies of the CSF2RA gene rs4129148 variant were GG, 40.2;GC,51.1; and CC, 8.7 % in cases and GG,39.2; GC,45.5; and CC,15.3 % in controls. The G allele frequency was 66% in cases and 62% in controls. Conclusion The IL3RA gene rs6603272 variant was not associated with schizophrenia(X2=0.271; P=0.873). However The CSF2RA gene rs4129148 variant CC genotype was associated with schizophrenia(X2=5.079; P=0.024). The G allele was agenetic risk factor for schizophrenia (X2=5.079; P=0.024; OR=1.895, 95%CI= 1.080- 3.326). The controls were in Hardy-Weinberg equilibrium. But cases were not.

EPA-0763 – IL3R gene RS6603272 variant and CSFR2A gene RS4129148 variant in patients with schizophrenia

Introduction Schizophrenia has genetic, epigenetic and environmental components. Recent reports showed that the IL3 gene, colony stimulating factor 2 receptor alpha (CSF2RA), beta (CSF2RB) and IL-3 receptor alpha (IL3RA), the IL-specific receptor subunits for CSF2 and IL3, respectively, are associated with schizophrenia. Aims Association analyses of rs6603272 variant of the IL3R gene and rs4129148 variant of CSFR2A gene with schizophrenia have been studied. Methods We had 166 schizophrenic patients and 246 healthy controls. In both case control studies, a PCR-RFLP method was used. Results The genoype frequencies of the IL3R gene rs6603272 variant were TT, 54.8, TG, 40.4, GG, 4.8 % in cases, TT, 57.7, TG, 36.2 and GG, 6.1% in controls. The frequency of T allele in controls and cases was 76% and 75% respectively. Similarly, the genotype frequencies of the CSFR2A gene rs4129148 variant were GG, 44.6; GC,39.8; CC,15.7 % in cases and GG,43.9; GC,43.1; and CC, 13.0% in controls. The G allele frequency was 64% in cases and 65% in controls. Conclusion In our study, we did not find an association between the rs66033272 variant of IL3RA gene and schizophrenia (χ2=0.896; P=0.639). Nor did we find an association between the CSFR2A rs4129148 variant and schizophrenia (χ2= 0.770; P=0.681)