Lack of association between variations of PDE4D and ischemic stroke in the Japanese population

Tomonaga Matsushita, Michiaki Kubo, Koji Yonemoto, Toshiharu Ninomiya, Kyota Ashikawa, Bailing Liang, Jun Hata, Yasufumi Doi, Takanari Kitazono, Setsuro Ibayashi, Mitsuo Iida, Yutaka Kiyohara, Yusuke Nakamura

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1245-1251
Number of pages7
JournalStroke
Volume40
Issue number4
DOIs
Publication statusPublished - 01-04-2009

Fingerprint

Single Nucleotide Polymorphism
Stroke
Haplotypes
Population
Japan
Genetic Markers
Infarction
Genes
Phenotype

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Matsushita, T., Kubo, M., Yonemoto, K., Ninomiya, T., Ashikawa, K., Liang, B., ... Nakamura, Y. (2009). Lack of association between variations of PDE4D and ischemic stroke in the Japanese population. Stroke, 40(4), 1245-1251. https://doi.org/10.1161/STROKEAHA.108.527408
Matsushita, Tomonaga ; Kubo, Michiaki ; Yonemoto, Koji ; Ninomiya, Toshiharu ; Ashikawa, Kyota ; Liang, Bailing ; Hata, Jun ; Doi, Yasufumi ; Kitazono, Takanari ; Ibayashi, Setsuro ; Iida, Mitsuo ; Kiyohara, Yutaka ; Nakamura, Yusuke. / Lack of association between variations of PDE4D and ischemic stroke in the Japanese population. In: Stroke. 2009 ; Vol. 40, No. 4. pp. 1245-1251.
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abstract = "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.",
author = "Tomonaga Matsushita and Michiaki Kubo and Koji Yonemoto and Toshiharu Ninomiya and Kyota Ashikawa and Bailing Liang and Jun Hata and Yasufumi Doi and Takanari Kitazono and Setsuro Ibayashi and Mitsuo Iida and Yutaka Kiyohara and Yusuke Nakamura",
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Matsushita, T, Kubo, M, Yonemoto, K, Ninomiya, T, Ashikawa, K, Liang, B, Hata, J, Doi, Y, Kitazono, T, Ibayashi, S, Iida, M, Kiyohara, Y & Nakamura, Y 2009, 'Lack of association between variations of PDE4D and ischemic stroke in the Japanese population', Stroke, vol. 40, no. 4, pp. 1245-1251. https://doi.org/10.1161/STROKEAHA.108.527408

Lack of association between variations of PDE4D and ischemic stroke in the Japanese population. / Matsushita, Tomonaga; Kubo, Michiaki; Yonemoto, Koji; Ninomiya, Toshiharu; Ashikawa, Kyota; Liang, Bailing; Hata, Jun; Doi, Yasufumi; Kitazono, Takanari; Ibayashi, Setsuro; Iida, Mitsuo; Kiyohara, Yutaka; Nakamura, Yusuke.

In: Stroke, Vol. 40, No. 4, 01.04.2009, p. 1245-1251.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lack of association between variations of PDE4D and ischemic stroke in the Japanese population

AU - Matsushita, Tomonaga

AU - Kubo, Michiaki

AU - Yonemoto, Koji

AU - Ninomiya, Toshiharu

AU - Ashikawa, Kyota

AU - Liang, Bailing

AU - Hata, Jun

AU - Doi, Yasufumi

AU - Kitazono, Takanari

AU - Ibayashi, Setsuro

AU - Iida, Mitsuo

AU - Kiyohara, Yutaka

AU - Nakamura, Yusuke

PY - 2009/4/1

Y1 - 2009/4/1

N2 - 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.

AB - 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.

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