PDE4D and stroke in the young. Genetic association of the SNP83T allele with ischaemic stroke in young stroke patients from Brescia (Italy) and Heidelberg (Germany)

Aims: Phosphodiesterases (PDE) are a large family of enzymes involved in the control of cAMP signaling. Several SNPs in the PDE4D gene were found to be significantly associated with ischemic stroke in the Icelandic population and a possible role of PDE4D in the development of atherosclerosis was discussed. In most, but not all, subsequent studies the association between PDE4D and stroke was confirmed, but results differed for stroke subtypes and for different SNPs within the 5'end of the PDE4D gene.

Methods: SNP83 of the PDE4D gene (rs966221) was analyzed in 202 young stroke patients (<50 years) from Brescia and in 140 young stroke patients from Heidelberg as well as in healthy controls series from both regions.

Results: In the series of patients from Heidelberg we found 56 (41%) CC, 68 (48%) CT and 16 (11%) TT, compared to 72 (36%) CC, 100 (49%) CT and 31 (15%) TT in healthy control subjects. Among the young stroke patients from Brescia we found 68 (34%) CC, 110 (54%) CT and 24 (12%) TT, compared to 50 (34%) CC, 72 (48%) CT and 27 (18%). Patients from both population carried less T-alleles (Chi-square p=0.090) and significantly less TT-genotypes (Chi-square p=0.021) than healthy control subjects.

Conclusions: Marker SNP83 was found significantly associated with ischemic stroke. Our data from two European series of young stroke patients and two matched control series are very similar to recent findings the Pakistani population. These data support a role for the Phosphodiesterase 4D gene in stroke pathogenesis.