In this study we aimed to assess the frequency of PDYN gene defects and extend the phenotype of SCA23 patients in a UK ataxia series and also in patients from Greece, Egypt and India.
We previously identified four missense mutations in the prodynorphin gene that cause human neurodegenerative disorder spinocerebellar ataxia type 23 (SCA23).
We have recently identified missense mutations in prodynorphin (PDYN), the precursor to dynorphin opioid peptides, as the cause for spinocerebellar ataxia (SCA23) in Dutch ataxia cases.
Thus, variations in the genes encoding both the kappa-opioid receptor and its ligand, OPRK1 and PDYN, are associated with the risk for alcohol dependence; this makes biological sense as variations in either should affect signaling through the kappa-opioid system.
Association with alcoholism was observed for rs2235751 and the presence of the minor allele G was associated with reduced DNA methylation at PDYN promoter in females and younger subjects.
These findings support the hypothesis that sequence variation in the PDYN gene contributes to both alcohol dependence and the induction of negative craving in alcohol-dependent subjects.
Thus, the data obtained suggest no association of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian population.
Fifteen percent (n=151) of the sample met DSM-IV criteria for alcohol dependence and while results did not support an association between the PDYN polymorphism and the diagnosis of alcohol dependence, we did observe an association between the "low" expressing L allele of the PDYN gene and a preference for engaging in disinhibited behavior.
In a nutshell, transition of a single nucleotide may modify differential DNA-protein interactions at OPRK1 and PDYN׳s SNPs, significantly associated with pathology that may lead to altered individual vulnerability for alcohol dependence.
Interfering with the trans-repression effect of downstream regulatory element antagonist modulator (DREAM) on the transcription of the opioid dynorphin-encoding prodynorphin (pdyn) gene might enhance pain relief in the periphery.
Pairwise tag single nucleotide polymorphisms (SNPs) in DREAM, PDYN and OPRK1 were genotyped in a UK population-based discovery cohort in whom pain was assessed using blank body manikins at three time points.