BACKGROUND AND PURPOSE: After the first genomewide association study of ischemic stroke identified PDE4D as a susceptible gene, many replication studies have been conducted. However, the validity of the association has remained controversial because of the heterogeneity of both genetic markers and phenotypes. METHODS: We investigated the association between variations of PDE4D and ischemic stroke by 3 methods: single-marker, haplotype, and tag-single nucleotide polymorphism (SNP) analyses. In the single-marker analysis, we evaluated the association using 2 large case-control samples (1112 cases and 1112 control subjects in a sample obtained from Kyushu, Japan, and 1711 cases and 1786 control subjects in BioBank Japan) and a prospective cohort with 14 years of follow-up. These samples were analyzed both separately and pooled. Haplotype and tag-SNP analyses were performed using the 2 case-control samples together. RESULTS: In single-marker association tests, we found no significant association in the same direction among the 6 SNP reported in the initial study and ischemic stroke subtypes. Haplotype analysis revealed no significant association between the region around the 5'-end of the gene and combined atherothrombotic and cardioembolic infarction. Rs7730070, a SNP located around the 3'-end of PDE4D, showed the lowest nominal probability value by tag-SNP analysis but was not significant after adjustment for multiple testing (adjusted probability value =0.36). CONCLUSIONS: These results suggest that variations in PDE4D are not associated with ischemic stroke risk in the Japanese population.
BACKGROUND AND PURPOSE: After the first genomewide association study of ischemic stroke identified PDE4D as a susceptible gene, many replication studies have been conducted. However, the validity of the association has remained controversial because of the heterogeneity of both genetic markers and phenotypes. METHODS: We investigated the association between variations of PDE4D and ischemic stroke by 3 methods: single-marker, haplotype, and tag-single nucleotide polymorphism (SNP) analyses. In the single-marker analysis, we evaluated the association using 2 large case-control samples (1112 cases and 1112 control subjects in a sample obtained from Kyushu, Japan, and 1711 cases and 1786 control subjects in BioBank Japan) and a prospective cohort with 14 years of follow-up. These samples were analyzed both separately and pooled. Haplotype and tag-SNP analyses were performed using the 2 case-control samples together. RESULTS: In single-marker association tests, we found no significant association in the same direction among the 6 SNP reported in the initial study and ischemic stroke subtypes. Haplotype analysis revealed no significant association between the region around the 5'-end of the gene and combined atherothrombotic and cardioembolic infarction. Rs7730070, a SNP located around the 3'-end of PDE4D, showed the lowest nominal probability value by tag-SNP analysis but was not significant after adjustment for multiple testing (adjusted probability value =0.36). CONCLUSIONS: These results suggest that variations in PDE4D are not associated with ischemic stroke risk in the Japanese population.
Authors: Håkan Lövkvist; Sandra Olsson; Peter Höglund; Olle Melander; Christina Jern; Marketa Sjögren; Gunnar Engström; J Gustav Smith; Bo Hedblad; Gunnar Andsberg; Hossein Delavaran; Katarina Jood; Ulf Kristoffersson; Holger Luthman; Bo Norrving; Arne Lindgren Journal: Eur J Hum Genet Date: 2012-01-25 Impact factor: 4.246
Authors: Ana M Peiró; Chih-Min Tang; Fiona Murray; Lingzhi Zhang; Loren M Brown; Daisy Chou; Laura Rassenti; Thomas J Kipps; Thomas A Kipps; Paul A Insel Journal: J Hum Genet Date: 2011-07-28 Impact factor: 3.172
Authors: Sunaina Yadav; Nazeeha Hasan; Thomas Marjot; Muhammad S Khan; Kameshwar Prasad; Paul Bentley; Pankaj Sharma Journal: PLoS One Date: 2013-03-07 Impact factor: 3.240