A PARK2 polymorphism associated with delayed neuropsychological sequelae after carbon monoxide poisoning
1 Department of Neurology, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, China
2 Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, No.388, Jianshe Middle Road, Xinxiang 453002, China
3 Health team of the 93123 unit, the Chinese People’s Liberation Army, Dalian, China
4 Xinxiang Central Hospital, Xinxiang, China
BMC Medical Genetics 2013, 14:99 doi:10.1186/1471-2350-14-99Published: 25 September 2013
Delayed neuropsychological sequelae (DNS) are the most severe and clinically intractable complications following acute carbon monoxide (CO) poisoning. Symptoms of DNS often resemble those of Parkinson’s disease (PD), suggesting shared neurological deficits. Furthermore, Parkinson protein 2 (PARK2) mutations are associated with PD and other neurodegenerative diseases. The association signal was detected between PARK2 and DNS after acute CO poisoning in our DNA pooling base genome-wide association study.
Two PARK2 single nucleotide polymorphisms (SNPs), rs1784594 (C/T allele) and rs1893895 (G/A allele), selected from DNA pooling base genome-wide association study, were genotyped by in 514 CO poisoning patients using polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLPs). The patient group consisted of 231 patients with DNS and 283 patients with no signs of lasting neurological damage (control population).
The frequency of the rs1784594 T allele was significantly lower in the DNS population (OR = 1.42, 95%CI: 1.08 − 1.87), as was the TT vs. CC genotype (OR = 1.95, 95%CI: 1.15 − 3.23) and the TT vs. CT + CC frequency (OR = 1.68, 95%CI: 1.32 − 2.49) compared to controls. Association analysis revealed a significant association between DNS and rs1784594 (P < 0.01) but not rs1893895 (P > 0.05). In female cases, the T allele frequency of rs1784594 was significantly lower in DNS patients compared to female controls (OR = 1.48, 95%CI: 1.01 − 2.17).
These data suggest that the allelic variant of rs1784594 is a risk factor for DNS following acute CO poisoning, especially in females. The PARK2 protein may modulate the susceptibility to DNS, underscoring the importance of examining the relationship between other PARK2 polymorphisms and clinical outcome following CO poisoning.