DNA repair genes in Parkinson's disease.
OBJECTIVE
There is a growing interest in the understanding of a possible role of DNA repair systems in ageing and neurodegenerative diseases after DNA damage is observed in the brain of individuals affected by neurodegenerative diseases. In the light of these findings, we investigated whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys) account for an increased risk of Parkinson's disease (PD).


METHODS
The present analyses are based on 60 case subjects with PD and 108 unrelated healthy controls. Genotyping of DNA repair gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism.


RESULTS
We, for the first time, demonstrated the positive association of APE1, XRCC1, and XRCC3 DNA repair gene variants with PD risk. In our study, the frequencies of Glu/Glu genotype in APE1, Gln+ genotype of XRCC1, and Thr+ genotype of XRCC3 are higher in patients than in controls (p=0.028, p=0.002 and p=0.046, respectively).


CONCLUSIONS
In conclusion, our findings have suggested that APE1, XRCC1, and XRCC3 genetic variants may be a risk factor by increasing oxidative stress that might cause the loss of dopaminergic cells in the substantiata nigra and locus caeruleus, leading to abnormal signal transmittion, and ultimately, the development of PD. In addition, generation of reactive oxygen species from dopamine might affect the other DNA repair pathway proteins that we did not examine in the current study. Further studies with larger sample groups are necessary to clarify the role of DNA repair genes and the development of PD.
Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
Mehmet
M
Gencer
Selcuk
S
Dasdemir
Bedia
B
Cakmakoglu
Yilmaz
Y
Cetinkaya
Figen
F
Varlibas
Hulya
H
Tireli
Cem Ismail
CI
Kucukali
Elif
E
Ozkok
Makbule
M
Aydin
D000368:Aged; D004260:DNA Repair / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase