A novel missense mutation in the UBE2A gene causes intellectual disability in the large X-linked family.

BACKGROUND: X-linked intellectual disability type Nascimento (XIDTN) is a disorder of the ubiquitin-proteasome pathway of protein degradation controlled by the UBE2A gene. The disease is characterized by intellectual disability, speech impairment, dysmorphic facial features, skin and nail anomalies, and, frequently, seizures. Eight affected males from a four-generation family who have intellectual disability and speech disorders were examined within an extended family of 57 individuals. Methods A number of methods were used for the molecular diagnosis. Conventional karyotype analyses, array-based comparative genomic hybridization (aCGH), whole exome swquencing (WES), sanger sequencing were performed. Results First, the conventional karyotype analyses were normal, and the results of the aCGH analyses were normal. Then, WES revealed a novel missense mutation of the UBE2A gene at exon 4 NM_003336.3: c.182A>G (p.Glu61Gly). Seven affected individuals and nine carriers in the multigenerational, large family were diagnosed through Sanger sequencing. CONCLUSIONS: We identified the mutation causing intellectual disability in the large family and demonstrated its phenotypic effects. Our cases showed that dysmorphic features could be considered mild, whereas intellectual disability and speech disorders are common features in XIDTN. The structure and function of the gene will be better understood in the novel UBE2A mutation. The genotype-phenotype correlation and phenotypic variations in XIDTN were identified through a literature review. Accordingly, XIDTN should be considered in individuals who exhibit an X-linked pedigree pattern and have intellectual disability and speech disorders.

Nigella sativa and Cancer: A Review Focusing on Breast Cancer, Inhibition of Metastasis and Enhancement of Natural Killer Cell Cytotoxicity.

BACKGROUND: In the last decade, there have been accumulating data that the use of medicinal plants could bring additional benefits to the supportive treatment of various diseases. Nigella sativa (N. sativa, family Ranunculaceae) is one of these plants that has attracted considerable interest. The extracts and seeds of N. sativa and its active component thymoquinone have been studied extensively and the results suggest that N. sativa might carry some therapeutic potential for many diseases, including cancer. METHODS: The selection criteria for references were applied through Pubmed with "N. sativa and cancer", "N. sativa and breast cancer", "N. sativa and metastasis", "N. sativa and cytotoxicity of natural killer cells". The pathway analysis was performed using the PANTHER tool by using five randomly selected N. sativa affected genes (Cyclin D1, P53, p21 protein (Cdc42/Rac) activated kinase 1 (PAK1), B-cell lymphoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF)) in order to elucidate further potentially affected signaling pathways. RESULTS: The aim of this review was to summarize studies regarding the effects of N. sativa in cancer generally, with a focus on breast cancer, its anti-metastatic effects, and how N. sativa modulates the cytotoxicity of Natural Killer cells that play a crucial role in tumor surveillance. CONCLUSION: In summary, the data suggest that N. sativa might be used for its anti-cancer and antimetastatic properties and as an immune system activator against cancer.

The Relationship Between Urothelial Type Bladder Cancer, Plasma 25-Hydroxyvitamin D Levels, and Vitamin D Receptor ApaI BsmI FokI, and TaqI Polymorphisms.

BACKGROUND: Bladder cancer is an important health problem which ranks 4th among most frequently seen cancer types in men. In our study we aimed to investigate the correlations among urothelial type bladder cancer polymorphisms, ApaI, BsmI, FokI, and TaqI, prevalently observed in the vitamin D receptor (VDR) gene and plasma vitamin D levels in a Turkish population. METHODS: Our study included 101 patients and 109 control subjects. Plasma 25(OH)D levels were determined using a HPLC method and VDR gene polymorphisms with PCR-RFLP method. RESULTS: A statistically significant intergroup difference was not observed with regard to age, gender, and BMIs of the patients. Median (min - max) 25(OH)D levels in the patient and the control groups were determined as 11.9 ng/dL (1.9 - 33.0 ng/dL) and 9.7 ng/dL (2.1 - 39.5 ng/dL), respectively. A statistically significant intergroup difference was not observed with regard to 25(OH)D levels (p = 0.402). A statistically significant intergroup differ-ence was not observed with regard to genotype distribution of ApaI, BsmI, and TaqI polymorphisms and allele frequencies. Control and urothelial type bladder cancer groups showed a statistically significant difference with respect to genotype distribution of FokI polymorphism (p = 0.048). However in a binary logistic regression model, when corrected OR values were estimated by including smoking history in the model, the correlation detected be-tween the presence of FF and increased risk of disease was not statistically significant (ORadj = 1.64, 95% CI = 0.89 - 3.02, p = 0.114). CONCLUSIONS: In the light of the data concerning Turkish population a statistically significant correlation could not be demonstrated between plasma vitamin D levels, ApaI, BsmI, FokI, and TaqI polymorphisms, and urothelial type bladder cancers. Since literature data are limited in number, further studies should be conducted in larger patient groups.

Female gender specific association of the Reelin (RELN) gene rs7341475 variant with schizophrenia.

RELN gene encodes a large extracellular matrix protein which is critical for neuronal migration, cell positioning and cell-cell interactions. It also controls the synaptic plasticity of neurons for initiation and maintenance of long term potentiation. The aim of this study is to investigate the association of RELN rs7341475 variant with schizophrenia. Genomic DNA isolation was performed from 105 schizophrenic patients and 137 healthy controls to determine RELN rs7341475 genotypes. Genotype and allele frequencies were determined by a polymerase chain reaction-restriction fragment length polymorphism method developed in our laboratory. Statistical analysis was performed using χ2 test. The frequencies for G allele were 79.5% in cases and 81.0% in controls, for A allele 20.5% in cases and 19.0% in controls in the overall population. The genotype frequencies of the RELN gene rs7341475 variant were GG; 63.8%, GA; 31.4% and AA; 4.8% in cases, GG; 63.5%, GA; 35.0% and AA; 1.5% in controls in the overall population. There was no statistically significant association between the rs7341475 variant of RELN gene and schizophrenia in the overall population (χ2 = 2.473, p = 0.290). In the gender specific analysis, female gender specific association was only found. The RELN rs7341475 variant GG genotype was significantly associated with schizophrenia (p = 0.034, OR 2.760, 95% CI 1.058-7.197) and A allele was protective against schizophrenia (p = 0.034, OR 0.362, 95% CI 0.139-0.945). All cases and controls were in Hardy-Weinberg equilibrium (p > 0.05). Population size can be increased to improve the statistical power. Moreover, other RELN gene variants which are especially involved in neuronal migration and epigenetic regulation may be analyzed for revealing the complex genetic architecture of schizophrenia. In conclusion, there was only association between the RELN rs7341475 variant and schizophrenia in the female gender in a Turkish population.

Pregnancy in Parkinson's disease with PARK2 mutations.

We report a pregnancy in a patient with Parkinson's disease with PARK2 mutations. Although pregnancy is uncommon in patients with Parkinson's disease, an early-onset Parkinson's patient with three silent and two missense mutations in the PARK2 gene is presented here.

A 2D mathematical model for tumor angiogenesis: The roles of certain cells in the extra cellular matrix.

We present a 2D mathematical model of tumor angiogenesis which is an extension of the 1D model originally presented in Levine et al. (2000) [1]. Our model is connected to that 1D model by some transmission and boundary conditions which carry certain cells, the endothelials, pericytes and macrophages from the vessel wall into the extra cellular matrix. In our extended model we also include a mechanism for the action of anti-angiogenic factors such as angiostatin. We present numerical simulations in which we obtain a very good "qualitative agreement" with the time of the onset of vascularization of tumors and with the fact that the capillary tip growth accelerates as it approaches the "tumor".

Nicotinamide-N-Methyltransferase gene rs694539 variant and migraine risk.

BACKGROUND: Migraine is a common neurovascular disorder affecting 10 to 20 % of the world population usually subdivided into migraine with auro (MA) and migraine without auro (MO). Homocysteine is involved in the pathophysiology of a number of neurological disorders. Elevated levels of homocysteine in the plasma is produced by the MTHFR gene rs 1801133 and rs 1801131 variants as well as the NNMT gene rs 694539 variant. METHODS: With the polymerase chain reaction-restriction fragment length polymorphism method developed recently in our laboratory, we were able to show an association between the NNMT gene rs694539 variant and migraine for the first time. RESULTS: Here we report the association of the Nicotinamide-N-methyltransferase gene (NNMT) rs694539 variant with migraine in a case-control study of 433 patients with migraine and 229 healthy controls (χ2 = 6.076, P = 0.048). After stratification, we were able only to show an association between the NNMT gene rs694539 variant and female patients with migraine on the genotype and allelic levels. However there was no association in male patients with migraine (χ2 = 1.054, P = 0.590). CONCLUSIONS: Consequently our results clearly indicate that the NNMT gene rs694539 variant is a genetic risk factor for migraine.

Transcription factor 4 gene rs9960767 polymorphism in bipolar disorder.

The transcription factor 4 (TCF4) gene encodes a helix-loop-helix transcription factor protein, which initiates neuronal differentiation and is primarily expressed during nervous system development. The aim of the present study is to investigate the association of the TCF4 rs9960767 polymorphism and bipolar disorder, which is highly heritable. DNA isolation was performed on 95 patients with bipolar disorder and 108 healthy control subjects to examine the TCF4 rs9960767 polymorphism. Genotypic and allelic frequencies were determined using the polymerase chain reaction-restriction fragment length polymorphism method designed in our laboratory. Statistical analysis was performed using χ2 test within the 95% confidence interval. Odds ratios were calculated and Hardy-Weinberg equilibrium (HWE) was verified for all control subjects and patients. The A allele frequency was 95.8% in the patients and 94.4% in the control subjects, and 4.2% in the patients and 5.6% in the control subjects for the C allele. The genotype frequencies of the TCF4 gene rs9960767 variant were as follows: AA, 91.6% and AC, 8.4% in patients with bipolar (CC genotype was not observed in cases); AA, 89.8%; AC, 9.3% and CC, 0.9% in the control subjects. No statistically significant difference was identified between the patients and control subjects (χ2=0.937; P=0.626). In addition, gender specific analysis was performed, although no significant association was found according to the gender distrubition. All patients and control subjects were in HWE (P>0.05). Statistical analysis of the data indicates that the TCF4 gene rs9960767 polymorphism is not an independent risk factor for bipolar disorder in the overall population or in terms of gender; however, an increased population size would improve the statistical power. Furthermore, additional gene variants that are specifically involved in neuronal development may be analyzed for revealing the complex genetic architecture of bipolar disorder. An improved approach would be better to evaluate the TCF4 gene in a pathway specific manner due to its role as a transcription factor.

Association of the nibrin gene (NBN) variants with breast cancer.

Nibrin, encoded by the NBN gene, participates in DNA repair. Mutations in the NBN gene lead to Nijemen breakage syndrome, which may result in several types of diseases, particularly susceptibility to cancer, including breast cancer. Polymorphic variants and defective mutations occurring in the NBN gene increase the risk of breast cancer through the double-stranded break repair mechanism. The aim of the present study was to investigate a possible association between breast cancer and NBN genetic variants, NBN 924 T>C, 8360 G>C and 30537 G>C, in women with breast cancer. Locus-specific primers were designed to study 3 genetic variants in DNA samples isolated from peripheral blood samples of 101 women with breast cancer and 115 healthy controls. Subsequently, 3 polymerase chain reaction-restriction fragment length polymorphism methods were performed and the obtained results were statistically analysed. The NBN gene 924 T>C variant was found to be significantly associated with breast cancer (χ2=5.722, P=0.017). There were no statistically significant differences between cases and controls in the NBN gene 8360 G>C variant (χ2=1,125, P=0.570) or the NBN gene 30537 G>C variant (χ2=4.301, P=0.116). In conclusion, the NBN gene 924 T>C variant may be a genetic risk factor for breast cancer development in women with breast cancer.

Association of Nicotinamide-N-Methyltransferase Gene rs694539 Variant with Epilepsy.

Here, we report the association of the rs694539 variant of nicotinamide-N-methyltransferase gene with epilepsy in a case-control study of 215 patients with epilepsy and 239 healthy controls (χ (2) = 11.641, P = 0.003). The individuals with the GG genotype revealed protection against epilepsy (χ (2) = 5.866, P = 0.015, OR = 0.623, 95 % CI = 0.425-0.915), whereas the individuals with the AA genotype showed statistically significant increased risk for epilepsy (χ (2) = 8.676, P = 0.003, OR = 5.479, 95 % CI = 1.553-19.337). In addition, the G allele was protective against epilepsy (χ (2) = 8.676, P = 0.003, OR = 0.183, 95 % CI = 0.052-0.644); on the contrary, the A allele was a genetic risk factor for epilepsy (χ (2) = 5.866, P = 0.015, OR = 1.604, 95 % CI = 1.093-2.354). Stratification analysis revealed that the association was statistically significant in male patients with epilepsy (χ (2) = 6.682, P = 0.035). However, the statistical power was only 0.33 in female patients with epilepsy (χ (2) = 5.275, P = 0.072). This finding, for the first time, suggests the involvement of the NNMT gene rs694539 variant in the etiology of epilepsy.

Association of rs62063857 variant of the saitohin gene with Parkinson's disease.

Saitohin gene found within the tau gene is thought to play a role in the pathogenesis of neurodegenerative diseases. The rs62063857 polymorphism originally found in the saitohin gene seems to be the responsible SNP in this event. This polymorphism is studied mostly in patients with Alzheimer's disease. Data on Parkinson's disease are scarce. Therefore, we examined the rs62063857 polymorphism in 583 Parkinson's disease patients (347 male and 236 female) and 396 healthy controls (238 male and 158 female) by a polymerase chain reaction and restriction fragment length polymorphism method to see whether it was associated with Parkinson's disease from the City of Istanbul, Turkey. The G allele frequency was 22 % in overall controls and 16 % in Parkinson's disease patients. In this study, the saitohin rs62063857 polymorphism was associated with Parkinson's disease (χ2 = 16.765; P = 0.000). Individuals with the AA genotype showed 1.7-fold increased risk for Parkinson's disease (χ2 = 16.680; P = 0.000), whereas individuals with the AG genotype revealed protection against Parkinson's disease (χ2 = 14.554; P = 0.000). After the stratification analysis according to gender, both male and female PD patients showed association with the alleles and genotypes of the rs62063857 polymorphism of the saitohin gene (χ2 = 9.476, P = 0.009; χ2 = 7.593, P = 0.022, respectively). When the Parkinson's patients were divided into two groups with regard to onset of the disease, both groups showed association with the disease. The Parkinson's patients with disease onset below 65 years of age showed 1.8-fold increased risk for the disease. The Parkinson's patients with disease onset over 65 showed more robust association with a 2.051-fold increased risk for the disease. Consequently, the rs62063857 polymorphism of the saitohin gene is a genetic risk factor for Parkinson's disease. Hence, this polymorphism may play a role in the etiology of Parkinson's disease.

Genetic variants in the PNPLA3 gene are associated with nonalcoholic steatohepatitis.

In this study, we report the association of the rs738407, rs738409, and rs2896019 variants of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) (adiponutrin) gene with nonalcoholic steatohepatitis (NASH) (χ(2)=14.528, p=0.001; χ(2)=18.882, p=0.000; χ(2)=7.449, p=0.024, respectively) in 80 patients with NASH and 303 healthy controls. We genotyped the subjects using three polymerase chain reaction-restriction fragment length polymorphism methods developed in our laboratory. Our findings confirm the findings of the recent case-control and genome-wide association studies carried out in different populations around the world. Thus, the three variants in PNPLA3 gene may be a genetic risk factor for 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.

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.

Heteromorphic variants of chromosome 9.

BACKGROUND: Heterochromatic variants of pericentromere of chromosome 9 are reported and discussed since decades concerning their detailed structure and clinical meaning. However, detailed studies are scarce. Thus, here we provide the largest ever done molecular cytogenetic research based on >300 chromosome 9 heteromorphism carriers. RESULTS: In this study, 334 carriers of heterochromatic variants of chromosome 9 were included, being 192 patients from Western Europe and the remainder from Easter-European origin. A 3-color-fluorescence in situ hybridization (FISH) probe-set directed against for 9p12 to 9q13~21.1 (9het-mix) and 8 different locus-specific probes were applied for their characterization. The 9het-mix enables the characterization of 21 of the yet known 24 chromosome 9 heteromorphic patterns. In this study, 17 different variants were detected including five yet unreported; the most frequent were pericentric inversions (49.4%) followed by 9qh-variants (23.9%), variants of 9ph (11.4%), cenh (8.2%), and dicentric- (3.8%) and duplication-variants (3.3%). For reasons of simplicity, a new short nomenclature for the yet reported 24 heteromorphic patterns of chromosome 9 is suggested. Six breakpoints involved in four of the 24 variants could be narrowed down using locus-specific probes. CONCLUSIONS: Based on this largest study ever done in carriers of chromosome 9 heteromorphisms, three of the 24 detailed variants were more frequently observed in Western than in Eastern Europe. Besides, there is no clear evidence that infertility is linked to any of the 24 chromosome 9 heteromorphic variants.

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.

Methylenetetrahydrofolate reductase gene polymorphisms in Turkish children with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common, multifactorial genetic disorder. The aim of the present study was to evaluate a possible association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and ADHD. There is evidence to suggest that MTHFR C677T and A1298C polymorphisms alter the function of the enzyme, causing reduced folate and increased homocysteine levels in plasma. Two polymorphisms of the MTHFR gene, C677T (rs1801133) and A1298C (rs1801131), were analyzed in a sample of 100 Diagnostic and Statistical Manual of Mental Disorders-IV-diagnosed ADHD and 300 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism method. We did not find any association between MTHFR 677T allele, MTHFR 1298C allele, and ADHD. In addition, there was no genotype association between the MTHFR gene and ADHD (χ(2)=1.711; df=2; p=0.425; χ(2)=2.946; df=2; p=0.229). Our data suggest that neither the MTHFR C677T polymorphism nor the MTHFR A1298C polymorphism was associated with ADHD in Turkish children. Thus, the MTHFR gene does not seem to play a role in the etiopathogenesis of ADHD in the cohort studied.