Association of common variation in the PPARA gene with incident myocardial infarction in individuals with type 2 diabetes

A Go-DARTS study

Alex S.F. Doney, Bettina Fischer, Simon Lee, Andrew D. Morris, Graham P. Leese, Colin N.A. Palmer

    Research output: Contribution to journalArticle

    30 Citations (Scopus)
    34 Downloads (Pure)

    Abstract

    Background: Common variants of the PPARA gene have been found to associate with ischaemic heart disease in non diabetic men. The L162V variant was found to be protective while the C2528G variant increased risk. L162V has also been associated with altered lipid measures. We therefore sought to determine the effect of PPARA gene variation on susceptibility to myocardial infarction in patients with type 2 diabetes. 1810 subjects with type 2 diabetes from the prospective Go-DARTS study were genotyped for the L162V and C2528G variants in the PPARA gene and the association of the variants with incident non-fatal myocardial infarction was examined. Cox's proportional hazards was used to interrogate time to event from recruitment, and linear regression for analysing association of genotype with quantitative clinical traits. Results: The V162 allele was associated with decreased risk of non-fatal myocardial infarction (HR=0.31, 95%CI 0.10-0.93 p=0.037) whereas the C2528 allele was associated with increased risk (HR=2.77 95%CI 1.34-5.75 p=0.006). Similarly V162 was associated with a later mean age of diagnosis with type 2 diabetes and C2582 an earlier age of diagnosis. C2528 was also associated with increased total cholesterol and LDL cholesterol, which did not account for the observed increased risk. Haplotype analysis demonstrated that when both rare variants occurred on the same haplotype the effect of each was abrogated. Conclusion: Genetic variation at the PPARA locus is important in determining cardiovascular risk in both male and female patients with diabetes. This genotype associated risk appears to be independent of the effect of these genotypes on lipid profiles and age of diagnosis with diabetes.

    Original languageEnglish
    Article number4
    Pages (from-to)1-7
    Number of pages7
    JournalNuclear Receptor
    Volume3
    Issue number4
    DOIs
    Publication statusPublished - 25 Nov 2005

    Fingerprint

    Type 2 Diabetes Mellitus
    Myocardial Infarction
    Genes
    Genotype
    Haplotypes
    Alleles
    Lipids
    LDL Cholesterol
    Myocardial Ischemia
    Early Diagnosis
    Linear Models
    Cholesterol

    Cite this

    @article{b314dfa54c99490f8e756b5031d6a33d,
    title = "Association of common variation in the PPARA gene with incident myocardial infarction in individuals with type 2 diabetes: A Go-DARTS study",
    abstract = "Background: Common variants of the PPARA gene have been found to associate with ischaemic heart disease in non diabetic men. The L162V variant was found to be protective while the C2528G variant increased risk. L162V has also been associated with altered lipid measures. We therefore sought to determine the effect of PPARA gene variation on susceptibility to myocardial infarction in patients with type 2 diabetes. 1810 subjects with type 2 diabetes from the prospective Go-DARTS study were genotyped for the L162V and C2528G variants in the PPARA gene and the association of the variants with incident non-fatal myocardial infarction was examined. Cox's proportional hazards was used to interrogate time to event from recruitment, and linear regression for analysing association of genotype with quantitative clinical traits. Results: The V162 allele was associated with decreased risk of non-fatal myocardial infarction (HR=0.31, 95{\%}CI 0.10-0.93 p=0.037) whereas the C2528 allele was associated with increased risk (HR=2.77 95{\%}CI 1.34-5.75 p=0.006). Similarly V162 was associated with a later mean age of diagnosis with type 2 diabetes and C2582 an earlier age of diagnosis. C2528 was also associated with increased total cholesterol and LDL cholesterol, which did not account for the observed increased risk. Haplotype analysis demonstrated that when both rare variants occurred on the same haplotype the effect of each was abrogated. Conclusion: Genetic variation at the PPARA locus is important in determining cardiovascular risk in both male and female patients with diabetes. This genotype associated risk appears to be independent of the effect of these genotypes on lipid profiles and age of diagnosis with diabetes.",
    author = "Doney, {Alex S.F.} and Bettina Fischer and Simon Lee and Morris, {Andrew D.} and Leese, {Graham P.} and Palmer, {Colin N.A.}",
    year = "2005",
    month = "11",
    day = "25",
    doi = "10.1186/1478-1336-3-4",
    language = "English",
    volume = "3",
    pages = "1--7",
    journal = "Nuclear Receptor",
    issn = "1478-1336",
    publisher = "BioMed Central Ltd.",
    number = "4",

    }

    Association of common variation in the PPARA gene with incident myocardial infarction in individuals with type 2 diabetes : A Go-DARTS study. / Doney, Alex S.F.; Fischer, Bettina; Lee, Simon; Morris, Andrew D.; Leese, Graham P.; Palmer, Colin N.A.

    In: Nuclear Receptor, Vol. 3, No. 4, 4, 25.11.2005, p. 1-7.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Association of common variation in the PPARA gene with incident myocardial infarction in individuals with type 2 diabetes

    T2 - A Go-DARTS study

    AU - Doney, Alex S.F.

    AU - Fischer, Bettina

    AU - Lee, Simon

    AU - Morris, Andrew D.

    AU - Leese, Graham P.

    AU - Palmer, Colin N.A.

    PY - 2005/11/25

    Y1 - 2005/11/25

    N2 - Background: Common variants of the PPARA gene have been found to associate with ischaemic heart disease in non diabetic men. The L162V variant was found to be protective while the C2528G variant increased risk. L162V has also been associated with altered lipid measures. We therefore sought to determine the effect of PPARA gene variation on susceptibility to myocardial infarction in patients with type 2 diabetes. 1810 subjects with type 2 diabetes from the prospective Go-DARTS study were genotyped for the L162V and C2528G variants in the PPARA gene and the association of the variants with incident non-fatal myocardial infarction was examined. Cox's proportional hazards was used to interrogate time to event from recruitment, and linear regression for analysing association of genotype with quantitative clinical traits. Results: The V162 allele was associated with decreased risk of non-fatal myocardial infarction (HR=0.31, 95%CI 0.10-0.93 p=0.037) whereas the C2528 allele was associated with increased risk (HR=2.77 95%CI 1.34-5.75 p=0.006). Similarly V162 was associated with a later mean age of diagnosis with type 2 diabetes and C2582 an earlier age of diagnosis. C2528 was also associated with increased total cholesterol and LDL cholesterol, which did not account for the observed increased risk. Haplotype analysis demonstrated that when both rare variants occurred on the same haplotype the effect of each was abrogated. Conclusion: Genetic variation at the PPARA locus is important in determining cardiovascular risk in both male and female patients with diabetes. This genotype associated risk appears to be independent of the effect of these genotypes on lipid profiles and age of diagnosis with diabetes.

    AB - Background: Common variants of the PPARA gene have been found to associate with ischaemic heart disease in non diabetic men. The L162V variant was found to be protective while the C2528G variant increased risk. L162V has also been associated with altered lipid measures. We therefore sought to determine the effect of PPARA gene variation on susceptibility to myocardial infarction in patients with type 2 diabetes. 1810 subjects with type 2 diabetes from the prospective Go-DARTS study were genotyped for the L162V and C2528G variants in the PPARA gene and the association of the variants with incident non-fatal myocardial infarction was examined. Cox's proportional hazards was used to interrogate time to event from recruitment, and linear regression for analysing association of genotype with quantitative clinical traits. Results: The V162 allele was associated with decreased risk of non-fatal myocardial infarction (HR=0.31, 95%CI 0.10-0.93 p=0.037) whereas the C2528 allele was associated with increased risk (HR=2.77 95%CI 1.34-5.75 p=0.006). Similarly V162 was associated with a later mean age of diagnosis with type 2 diabetes and C2582 an earlier age of diagnosis. C2528 was also associated with increased total cholesterol and LDL cholesterol, which did not account for the observed increased risk. Haplotype analysis demonstrated that when both rare variants occurred on the same haplotype the effect of each was abrogated. Conclusion: Genetic variation at the PPARA locus is important in determining cardiovascular risk in both male and female patients with diabetes. This genotype associated risk appears to be independent of the effect of these genotypes on lipid profiles and age of diagnosis with diabetes.

    UR - http://www.scopus.com/inward/record.url?scp=28844489398&partnerID=8YFLogxK

    U2 - 10.1186/1478-1336-3-4

    DO - 10.1186/1478-1336-3-4

    M3 - Article

    VL - 3

    SP - 1

    EP - 7

    JO - Nuclear Receptor

    JF - Nuclear Receptor

    SN - 1478-1336

    IS - 4

    M1 - 4

    ER -