Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.
Twelve GSK3B tag single-nucleotide polymorphisms (SNPs), together with the previously AD-associated rs334558, were analyzed in 583 AD patients and 673 controls.
However, the analysis of rs334558 revealed that the risk of PD decreased in heterozygote, dominant or additive models (OR=0.60, 95% CI: 0.48, 0.74; OR=0.63, 95% CI: 0.51, 0.78; OR=0.82, 95% CI: 0.71, 0.94, respectively) from the Eastern Asian population.
Moreover, the analysis on the homozygote, heterozygote, dominant or additive models suggested that rs6438552 also reduced the PD risk (OR=0.45, 95% CI: 0.24, 0.84; OR=0.62, 95% CI: 0.39, 0.97; OR=0.57, 95% CI: 0.37, 0.87; OR=0.66, 95% CI: 0.49, 0.88, respectively) in the Eastern Asian population.
To determine their potential role in the pathogenesis of Parkinson's disease (PD) we analyzed 2 functional single nucleotide polymorphisms (SNPs) of GSK3B (rs334558 and rs6438552) and rs735555 of CDK5 regulatory subunit 1 (CDK5R1) in 373 PD cases and 346 healthy controls of eastern India.
However, little is known about the potential role of the GSK-3β rs334558 polymorphism, which has been associated with amnestic mild cognitive impairment (aMCI), which is itself associated with a high risk of AD.
However, among these interactions, individuals carrying the (C/C) genotype at both loci (rs6438552 and rs735555) had almost twice the risk of developing PD than those without this genotypic combination (OR, 1.871; 95% CI, 1.181-2.964; p = 0.009).
The minor allele (T) of the promoter rs334558 within GSK3B was associated with an increased risk of LOAD (odds ratios/OR=1.381, P=0.006), T carriers may be easier to develop AD (P=0.002, power=0.92).
In our study, the MAPT H1 haplotype was found to be significantly associated with PD, no association was detected between the intronic rs6438552 (-157 T/C) GSK3β polymorphism and PD, whereas the C/C genotype of the promoter rs334558 (-50 T/C) GSK3β polymorphism was found to exert a protective role.
Subjects carrying both the HO-1 (-413, rs2071746) TT genotype and the GSK3beta (-157, rs6438552) TT genotype had a four times higher risk of developing PD than subjects without these genotypes (adjusted by age and sex OR = 4.12; 95% CI = 1.45-11.71; Bonferroni corrected P = 0.024).
Subjects carrying both the CDK5R1 (3'-UTR, rs735555) AA genotype and the GSK-3beta (-50, rs334558) CC genotype had a 12.5-fold decrease in AD risk (adjusted by age, sex and APOE status OR = 0.08, 95% CI = 0.01-0.76, P = 0.03), suggesting synergistic effects (epistasis) between both genes.