ABSTRACT
Mutations in the PINK1 gene (PARK6), a putative serine-threonine kinase, cause autosomal recessive Parkinson's disease. PINK1 functions as a protein kinase and confers protective effects in the mitochondria, where it is primarily located. We assessed in a population of European ancestry whether common genetic variation in this novel gene influences nonmendelian forms of Parkinson's disease. We defined the linkage disequilibrium structure of PINK1 and used this to identify a set of tagging single nucleotide polymorphisms that we estimate will efficiently represent all of the common DNA variation in the entire gene. Genotyping these tags in a set of 576 Parkinson's disease patients and 514 controls did not demonstrate a case-control partition for allele or for haplotype and thus provides evidence against the existence of a common functional variants in PINK1 that has a strong influence on PD risk.
Subject(s)
Parkinson Disease/enzymology , Parkinson Disease/genetics , Protein Kinases/genetics , Adult , Aged , Female , Genetic Linkage , Genetic Variation , Genotype , Haplotypes/genetics , Humans , Male , Middle Aged , Parkinsonian Disorders/enzymology , Parkinsonian Disorders/genetics , Polymorphism, Single Nucleotide , Protein Kinases/physiologyABSTRACT
Heat shock proteins (hsp) represent a group of chaperones which protects the cells against a diversity of stresses. It has been demonstrated that hsp27 is constitutively present in cells where it plays an important role in different cytoprotective processes which ultimately inhibit cell death. We investigated the response of the isolated perfused mouse heart over expressing hsp27 to the ischaemia/reperfusion injury using infarct size as an end point. Our results show for the first time that mice over expressing hsp27 (verified by Western blotting analysis) were found to be protected from lethal ischaemia/reperfusion injury compared to their negative littermates.
