Tumor necrosis factor alpha gene rs1799724 polymorphism in Alzheimer's disease.

Neurofibrillar tangles formed by the accumulation of hyperphosphorylated tau proteins in the intracellular space and the senile plaques formed by amyloid ß (Aß) accumulating in extracellular environment are shown as two main elements of Alzheimer's disease (AD). In our study, the relationship between the risk of Alzheimer's disease and TNFα rs1799724 polymorphism in the Turkish population was investigated. Our study is the first report investigating the relationship between the risk of Alzheimer's disease and TNFα rs1799724 gene polymorphism in Turkish population. No significant relation was found for rs1799724 polymorphism in AD patients. Since TNFα rs1799724 gene polymorphism was also associated with type 2 diabetes mellitus (T2DM), the polymorphism also was evaluated in T2DM within the AD patients group. According to our results rs1799724 polymorphism was found to be a significant relationship with T2DM within AD patients group. On the other hand, there was no significant difference between fasting blood glucose values of AD patients and -857C>T (rs1799724) polymorphism. According to our results, -857C>T rs1799724 polymorphism may have a relationship with T2DM as independent from AD.

The p.Thr11Met mutation in c19orf12 is frequent among adult Turkish patients with MPAN.

INTRODUCTION: Mutations in the C19orf12 gene cause mitochondrial membrane protein associated neurodegeneration (MPAN), an autosomal recessive form of neurodegeneration with brain iron accumulation (NBIA). A limited number of patients with C19orf12 mutations, particularly those with adult onset of symptoms, have been reported. METHODS: We sequenced the entire coding region of C19orf12 in 15 Turkish adult probands with idiopathic NBIA. We also performed haplotype analysis in families with a recurrent C19orf12 mutation. Clinical features were collected using a standardized form. RESULTS: Nine of our 15 probands (60%) carried the homozygous c.32C > T mutation in C19orf12 (predicted protein effect: p.Thr11Met). This homozygous mutation co-segregated with the disease in all affected relatives available for testing (16 homozygous subjects). Haplotypes across the C19orf12 locus were identical for a very small region, closest to the mutation, suggesting an old founder, or, two independent founders. The clinical phenotype was characterized by adult onset in most cases (mean 24.5 years, range 10-36), and broad spectrum, including prominent parkinsonism, pyramidal signs, psychiatric disturbances, cognitive decline, and motor axonal neuropathy, in various combinations. On T2- or susceptibility weighted-MRI images, all patients displayed bilateral hypointensities in globus pallidus and substantia nigra, without an eye-of-the-tiger sign; however, hyperintense streaking of the medial medullary lamina between the external and internal parts of globus pallidus was observed frequently. CONCLUSION: The C19orf12 p.Thr11Met mutation is frequent among adult Turkish patients with MPAN. These findings contribute to the characterization of this important NBIA form, and have direct implications for genetic testing of patients of Turkish origin.