Dopamine β-hydroxylase −1021C>T association and Parkinson's disease

Abstract

A single nucleotide polymorphism in the promoter region of the dopamine β-hydroxylase gene (DBH -1021C>T; rs1611115) is reported to regulate plasma enzyme activity levels. This variant has also been the focus of two large association studies in Parkinson's disease yielding conflicting results. We examined this association in four Caucasian patient-control series (n=2696). A modest protective association was observed in the Norwegian series (OR=0.81, p=0.03; n=1676), however the effect was in the opposite direction in the Polish series (OR=2.01, p=0.01; n=224). No association was observed for DBH -1021C>T with disease susceptibility in the US and Irish series, or combining all four series (OR=0. 91, p=0.16, n=2696). We observed a modest association between DBH -1021C>T and AAO in the combined series (p=0.01). Taken together, these findings indicate that DBH -1021C>T does not play a major role in the pathogenesis of Parkinson's disease.

Association of Dopamine Beta-Hydroxylase Polymorphisms with Alzheimer’s Disease, Parkinson’s Disease and Schizophrenia: Evidence Based on Currently Available Loci

“…For rs1611115, combined results from all four of the studies included indicated that this SNP is not statistically associated with an increased PD risk, consistent with the results from two individual studies authored by Chun L.S. et al (2007) [28] and Ross O. et al (2008) [30] but not with those of the other two studies (Fig. 2B).…”

“…These studies were published from 1996 to 2016. Among them, 25 studies involved Caucasian populations (AD: n = 5 [20][21][22], PD: n = 3 [28][29][30], SCZ: n = 17 [34-37, 44-46, 48]), and 16 studies involved Asian populations (AD: n = 2 [23,24], PD: n = 4 [31][32][33], SCZ: n = 10 [38-43, 47, 49]). Additionally, two diagnostic criteria were used among the AD studies included (DSM-IV [56] and NINCDS-ADRDA [57]), two criteria were used for PD studies (UK PD Society Brain Bank Clinical Diagnostic Criteria (UK-PDSBB) [58] and Standard for Second National conference on Cone Diseases), and three criteria were used for SCZ studies (DSM-IV [56], DSM-III-R [56] and ICD-10 [59]).…”

“…Many GWAS and case-control studies have investigated the relationship of DBH polymorphisms with these three diseases, and it was even reported that DBH polymorphisms, such as variations in exons of rs1108580, rs5320, MspI, and rs4531 and introns of 5'-Ins/Del, rs1611115, rs1611131, and rs2519152, could play a role in the pathophysiologies of AD [20][21][22][23][24], PD [28][29][30][31][32][33] and SCZ [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. [28,30]; however, a recent genetic association research by Shao P. et al in 2016 indicated that the TT genotype may lead to a higher risk of PD occurrence than the common genotype CC [31]. Conflicting results have also been published on variations of DBH rs2519152 [31] and other loci [29,31].…”

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

“…Of the staggering 8031 reported polymorphisms, less than 20 have been positively associated with the disease; however, the functional implications of these polymorphisms are unclear (Table ) (Tang et al ; Tang et al ; Ross et al ; Kamata et al ; Cubells et al ; Mustapic et al ). Of the total genetic variants, over 7000 are upstream/downstream or within intronic elements.…”

“…Comprehensive meta‐analyses, compiling data from multiple ethnicities, have shown that this polymorphism may not be associated with PD. Interestingly, however, authors suggest that this SNP has been linked with a delay in the age of onset of PD in several different studies (Ross et al ; Kang et al ). Ross and co‐workers suggest that this may be because of higher availability of DA in the earlier stages of the disease, yielding the belief that lower DβH levels may be protective (Ross et al ).…”