ALU-INSERTION Yb8NBC36 IN THE KCNJ6 GENE
IS A RISK FACTOR FOR PARKINSON’S DISEASE
Gilyazova I1,*, Khidiyatova I1, Akhmetova V1, Baitimerov A2, Magzhanov R2, Khusnutdinova E1 *Corresponding Author: Dr. Irina Gilyazova, Department of Human Genomics, Institute of Biochemistry and Genetics, Ufa Science Center, Russian Academy of Sciences, 71 Prospekt Oktyabrya, Ufa 450054, Russia; Tel.: +7(3472)356088; Fax: +7(3472)356100; E-mail: gilyasova_irina@mail.ru
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INTRODUCTION
Parkinson’s Disease (PD) is a slowly progressive neurodegenerative disorder with typical clinical features, such as resting tremor, cogwheel rigidity, bradykinesia, and postural instability. It is due to the relatively selective loss of dopaminergic neurons in the substantia nigra pars compacta, which leads to profound reduction in striatal dopamine (DA). It is the second most frequent neurodegenerative disorder after Alzheimer’s Disease, with a prevalence of 1-2% in people over the age of 50 years. The frequency of PD in the Bashkortostan Republic varies from 3.2 to 117 per 100,000 adults. In the overwhelming majority of PD patients, the disease has been thought to occur sporadically. But there is increasing evidence for a genetic contribution to the disorder [1,2]. Genetic susceptibility factors acting together with environmental exposure may lead to the development of this late-onset disease. Thus, molecular-genetic studies that identify causative genes and susceptibility alleles of PD may elucidate the molecular pathways of the development of PD.
Animal models can play an important role in detecting genetic defects that lead to the disease. One model for PD is the homozygous weaver mouse, a mutant mouse strain, which displays progressive postnatal depletion of dopaminergic cells in the mesencephalon and age-dependent dopaminergic neuronal loss [3-7]. A homozygous mutation in the H5 pore region of mGIRK2, a putative G-protein inward rectifier K+ channel, is responsible for the weaver mouse [8]. The human homologue of mGIRK2, also known as KCNJ6, KIR3.2, BIR1, KATP2 or KCNJ7, has been mapped to chromosome 21q22 [4,5]. The G-protein-gated inwardly rectifying potassium channels are found in neurons, atrial myocytes and neuroendocrine cells [9], and are characteristically activated by Gi/o-coupled receptors. A possible involvement of this gene in the pathogenesis of PD has been discussed [6,7].
In recent years, Alu-insertion polymorphisms have been intensively investigated in different populations, and in human genetics have been proposed to contribute to many human diseases. Deininger and Batzer [10] have found 16 examples of diseases caused by the insertion of Alu-elements, suggesting that they may contribute to about 0.1% of all human genetic disorders, including neurofibromatosis, Apert’s Syndrome, cholinesterase deficiency, hypocalciuric hypercalcemia, breast cancer and hereditary desmoid disease.
The aim of our study was to determine the association of the Alu-insertion Yb8NBC36 in the human inwardly-rectifying K-channel gene (KCNJ6) with occurrence of idiopathic PD in patients from the Bashkorostan Republic. It is a republic within the Russian Federation that is located in the Volga-Ural region, at the border of Europe and Asia. Bashkortostan is comprised of inhabitants of various ethnic origins; 36.32% of inhabitants are Russians, 29.76% Bashkirs, 24.14% Tatars, and the remaining 9.78% are Chuvashes, Maris, Ukrainians, Udmurts, Belorussians, etc. (All-Russia Census, 2002).
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