Mutations, deletions, and polymorphisms of the PARK2 gene have been associated with PD, cancer, susceptibility to bacterial infections, and other diseases [9, 18–20]. Recently, a number of SNPs within PARK2 have been identified that are possible risk factors for PD [21–23]. Furthermore, early-onset PD, autism spectrum disorder, and progressive supranuclear palsy have also been associated with PARK2 mutations [24–26], suggesting that these PARK2 mutations disrupt neural development or decrease resistance to insult, leading to developmental deficits or increasing susceptibility to diseases such as DNS following CO poisoning.
In contrast to neurodegenerative diseases, most studies on DNS following CO poisoning have focused on clinical characteristics, and few studies have attempted to link the propensity for DNS with specific genotypes [7, 27–29]. Our case–control study suggests that an allelic variant of PARK2, the rs1784594 polymorphism, might influence DNS risk in a Han population from Northern Henan, China.
We measured the genotype frequencies of two PARK2 polymorphisms, rs1784594 and rs1893895, and found that the C variant of rs1784594 may be a risk factor for DNS. The allele frequencies indicated that the TT genotype might lower the risk for DNS after CO poisoning by 1.7-fold compared to CC + CT. This suggested that the T allele of rs1784594 may confer resistance against DNS through some as yet unknown neuroprotective mechanism. There was also a significant association between C/T allele distribution and clinical outcome in females, but not with any specific genotype. No significant association was found between hypertension status and DNS risk. Even after controlling for hypertension, rs1893895 variant, and sex, the rs1784594 remained a significant risk factor for DNS following CO poisoning.
To determine the gender effect, genotype and allele frequency in both sexes were assessed. The female DNS cases exhibited a significant difference in allele frequencies of rs1784594 compared to female controls. But there is no significant interaction between SNP and sex. DNS was a disease resulting from interactions between environmental factors (CO) and an individual’s biological background. The aim of this study was to explore genetic susceptibility about the normal human’s different consequences after poisoning. The different caused by gender effect is hard to ignore, especially in endocrine, development, autoimmunity and stress reaction. Sex-specific association was often reported in other psychosis. The female-specific association may be attributed to the interaction between estrogen and genes related to brain development.