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Here is a bit of data:<!64:45> <HTML><HEAD><TITLE>Documents:NADH dehydrogenase and CYP2D6 genotypes in Parkinso n's disease</TITLE></HEAD> <BODY> [<a href="0064.html">prev</a>] [<a href="0045.html">next</a>][<A HREF="/cgi-bin/ documents.pl?searchmask0">Search</A>] <BR> [<a href="index.html">by subject</a>] [<a href="author.html">by author</a>]<br> <H1> <H3><IMG SRC="/HUM-MOLGEN/gif/page1.gif" alt=""> Neurogenetics</H3> NADH dehydrogenase and CYP2D6 genotypes in Parkinson's disease </H1><H2>S. Kvsel, N.M. Schnopp, R. Egensperger, P. Mehraein and M.B. Graeber</H 2> Molecular Neuropathology Laboratory and Reference Center for Neurodegenerative D isorders, Institute of Neuropathology, Ludwig-Maximilians-University, Thalkirch ner Str. 36, 80337 Munich, Germany<P> <I>2nd Workshop Neurogenetics in Germany, Munich, October 19-21, 1995</I><P> <B>Abstract</B><BR> Several mutations of mitochondrial DNA (mtDNA) and polymorphisms of the debriso quine 4-hydroxylase gene (CYP2D6) have been associated with an increased susceptibilit y to Parkinson's disease (PD). We have studied 21 neuropathologically verified cases of PD and 89 controls. Genomic DNA was extracted from formalin-fixed, paraffin-embe dded brain tissue as well as from freshly frozen tissue blocks and amplified using th e polymerase chain reaction. PCR products were analyzed by restriction enzyme dige stion and direct non-radioactive cycle sequencing. Degrees of mtDNA heteroplasmy were determined using laser densitometry. Ratios of mtDNA carrying the 4977 bp "commo n deletion" were quantified by competitive PCR. 4 out of 21 PD brains (5/77 contro ls) showed a heteroplasmic mtDNAG5460A transition which affects the ND2 subunit gene of complex I. Degrees of heteroplasmy for this point mutation ranged from less tha n 5 to more than 95%. One PD brain was homoplasmic for the mtDNAA4336G transition af fecting the mitochondrial tRNAGln. In contrast, levels of the 4977 bp deletion were not increased in the substantia nigra of PD brains. Allelic frequencies at the CYP2D 6 locus (CYP2D6G1934A and CYP2D6C2938T) were comparable in PD cases and controls. One PD brain was homozygous for the CYP2D6C2938T allele. Our results show that patie nts with Lewy-body parkinsonism exhibit genetic heterogeneity at candidate susceptib ility loci. Our findings are in line with the concept that a definable number of interindividually variable genetic defects may confer increased susceptibility to PD. Systematic sequencing studies will help to clarify whether mitochondrial point mutations are responsible for the complex I defect observed in PD.<BR><BR> Supported by the Deutsche Forschungsgemeinschaft (Gerhard Hess-Programm). <P> <B>Headings</B><BR>Parkinson's disease (PD)<BR>NADH dehydrogenase<BR>CYP2D6 geno types<P> <P> <B>For further information please contact:</B><BR> <a href="mailto: "> </a><br> <br> <br> <br> <HR> <A HREF="/HUM-MOLGEN/"><IMG SRC="/Images/buttons/go_top_btn.gif" ALIGN=MIDDLE BORDER=0 WIDTH=40 HEIGHT=40 ALT="Back"> HUM-MOLGEN</A> <HR><address>Posted by: (Zollmann) Host: andros.informatik.uni-rostock.de date : September 06, 95 13:51:33<BR>Generated by <A HREF="http://wwwdb.informatik.uni- rostock.de/Kai/doc/meetings/">meetings and positions 1.0</A> by <a href="http: //wwwdb.informatik.uni-rostock.de/Kai/">Kai Garlipp</a></ADDRESS>