No Association of Functional Polymorphisms in Methlylenetetrahydrofolate Reductase and the Risk and Minor Physical Anomalies of Schizophrenia in Korean Population

Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia

Child with Deletion 9p Syndrome Presenting with Craniofacial Dysmorphism, Developmental Delay, and Multiple Congenital Malformations

A 4-month-old Sri Lankan male child case with a de novo terminal deletion in the p22 → pter region of chromosome 9 is described. The child presented with craniofacial dysmorphism, developmental delay, and congenital malformations in agreement with the consensus phenotype. A distinctive feature observed in this child was complete collapse of the left lung due to malformation of lung tissue. Cytogenetic studies confirmed terminal deletion of the short arm of chromosome 9 distal to band p22 [46,XY,del(9)(p22 → pter)]. This is the first reported case of a de novo deletion 9p syndrome associated with pulmonary hypoplasia. This finding contributes to the widening of the spectrum of phenotypic features associated with deletion 9p syndrome

Combined effect of CCND1 and COMT polymorphisms and increased breast cancer risk

<p>Abstract</p> <p>Background</p> <p>Estrogens are crucial tumorigenic hormones, which impact the cell growth and proliferation during breast cancer development. Estrogens are metabolized by a series of enzymes including COMT, which converts catechol estrogens into biologically non-hazardous methoxyestrogens. Several studies have also shown the relationship between estrogen and cell cycle progression through activation of CCND1 transcription.</p> <p>Methods</p> <p>In this study, we have investigated the independent and the combined effects of commonly occurring CCND1 (Pro241Pro, A870G) and COMT (Met108/158Val) polymorphisms to breast cancer risk in two independent Caucasian populations from Ontario (1228 breast cancer cases and 719 population controls) and Finland (728 breast cancer cases and 687 population controls). Both COMT and CCND1 polymorphisms have been previously shown to impact on the enzymatic activity of the coded proteins.</p> <p>Results</p> <p>Here, we have shown that the high enzymatic activity genotype of CCND1^High(AA) was associated with increased breast cancer risk in both the Ontario [OR: 1.3, 95%CI (1.0–1.69)] and the Finland sample [OR: 1.4, 95%CI (1.01–1.84)]. The heterozygous COMT^Medium(MetVal) and the high enzymatic activity of COMT^High(ValVal) genotype was also associated with breast cancer risk in Ontario cases, [OR: 1.3, 95%CI (1.07–1.68)] and [OR: 1.4, 95%CI (1.07–1.81)], respectively. However, there was neither a statistically significant association nor increased trend of breast cancer risk with COMT^High(ValVal) genotypes in the Finland cases [OR: 1.0, 95%CI (0.73–1.39)]. In the combined analysis, the higher activity alleles of the COMT and CCND1 is associated with increased breast cancer risk in both Ontario [OR: <b>2.22</b>, 95%CI (1.49–3.28)] and Finland [OR: <b>1.73</b>, 95%CI (1.08–2.78)] populations studied. The trend test was statistically significant in both the Ontario and Finland populations across the genotypes associated with increasing enzymatic activity.</p> <p>Conclusion</p> <p>Using two independent Caucasian populations, we have shown a stronger combined effect of the two commonly occurring CCND1 and COMT genotypes in the context of breast cancer predisposition.</p

Using global team science to identify genetic parkinson's disease worldwide.

No abstract available

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 (chi (2) = 11.641, P = 0.003). The individuals with the GG genotype revealed protection against epilepsy (chi (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 (chi (2) = 8.676, P = 0.003, OR = 5.479, 95 % CI = 1.553-19.337). In addition, the G allele was protective against epilepsy (chi (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 (chi (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 (chi (2) = 6.682, P = 0.035). However, the statistical power was only 0.33 in female patients with epilepsy (chi (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

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

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 (chi(2) = 1.711; df = 2; p = 0.425; chi(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