A large-sample assessment of possible association between ischaemic stroke and rs12188950 in the PDE4D gene

Abstract

Previous reports have shown ambiguous findings regarding the possible associations between ischaemic stroke (IS) and single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) gene region. The SNP rs12188950 (or SNP45) has often been studied in this context. We performed a multi-centre study involving a large sample of 2599 IS patients and 2093 control subjects from the south and west regions of Sweden to replicate previous studies regarding IS risk and rs12188950. Subjects from Lund Stroke Register (LSR), Malmö Diet and Cancer Study (MDC) and Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) were enroled. Subgroups of participants with hypertension and participants o55 years of age, as well as the TOAST subgroups large vessel disease, small vessel disease and cardioembolism, were also assessed. Univariate odds ratios (ORs) and ORs controlling for hypertension, diabetes and current smoking were calculated. We additionally performed a meta-analysis including 10 500 patients and 10 102 control subjects from 17 publications (including the present study). When assessing pooled data from LSR, MDC and SAHLSIS we obtained no association between IS and rs12188950 for all participants (OR¼0.93; 95% confidence interval (CI): 0.83-1.05). Significant associations were not found for hypertensive participants or participants with age o55, or when separately evaluating patients from the three different TOAST subgroups. The meta-analysis showed no significant overall estimate (OR¼0.96; 95% CI: 0.89-1.04) with significant heterogeneity for random effect (P¼0.042). No effect from rs12188950 on IS was found from either our pooled multi-centre data or the performed meta-analysis. We did not find any association between the examined subgroups and rs12188950 either.

Different mutations inPDE4Dassociated with developmental disorders with mirror phenotypes

“…Metabolic and cardiovascular manifestations, including hypertension, have also been reported 20. In addition, genome-wide association studies have suggested PDE4D as a candidate gene in ischaemic stroke 21. One acrodysostosis patient in our study suffers from severe hypertension requiring medication, one has diabetes type 1 and another patient has been investigated for suspected deep vein thrombosis (table 3).…”

Are 25 SNPs from the CARDIoGRAM study associated with ischaemic stroke?

“…We included 3986 patients with IS and 2459 control subjects from three Swedish hospital centers: Lund Stroke Register (LSR), Malm€ o Diet and Cancer Study (MDC) and the Sahlgrenska Academy Study on Ischaemic Stroke (SAHLSIS) [10,11,[21][22][23][24][25][26][27].…”

Association of phosphodiesterase 4D gene and interleukin-6 receptor gene polymorphisms with ischemic stroke in a Chinese hypertensive population

“…However, there are relatively limited studies on this association. A study by Liao et al (2010) demonstrated that there was a significant association between rs12188950 and ischemic stroke, but no such correlation was found in a large sample population study conducted in Sweden (Lovkvist et al, 2012). The rs12188950 polymorphism in PDE4D has been shown to be a protective factor for ischemic stroke in other populations (Lovkvist et al, 2008).…”

“…Hence, the rs12188950 polymorphism did not exist in the current study population. A study of Caucasians and African-Americans in the US also has shown that there was no polymorphism of rs12188950 (Lovkvist et al, 2012). Recently, a study on hospitalized Chinese patients was conducted, and the authors concluded that the rs918592 polymorphism was significantly associated with ischemic stroke (Song et al, 2012).…”