PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

Ulla Vogel, Stine Segel, Claus Dethlefsen, Anne Tjønneland, Anne Thoustrup Saber, Håkan Wallin, Majken Karoline Jensen, Erik Berg Schmidt, Pall Skytt Andersen, Kim Overvad

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPAR gamma 2 Pro(12)Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPAR gamma activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine.

    Methods: A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals.

    Results: Homozygous male variant allele carriers of PPAR gamma 2 Pro(12)Ala were at higher risk of ACS (HR = 2.12, 95% CI: 1.00-4.48) than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5-38.7) compared to homozygous common allele carriers (p for interaction < 0.0001). Overall, the association was only observed among homozygous variant allele carriers. Thus, all the observed associations were obtained in subgroups including small numbers of cases. It is therefore possible that the observed associations were due to chance.

    Conclusion: In the present study, there were no consistent associations between PPAR gamma Pro(12)Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.

    OriginalsprogEngelsk
    TidsskriftBMC Medical Genetics
    Vol/bind10
    ISSN1471-2350
    DOI
    StatusUdgivet - 2009

    Citer dette

    Vogel, U., Segel, S., Dethlefsen, C., Tjønneland, A., Saber, A. T., Wallin, H., ... Overvad, K. (2009). PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes. BMC Medical Genetics, 10. https://doi.org/10.1186/1471-2350-10-52
    Vogel, Ulla ; Segel, Stine ; Dethlefsen, Claus ; Tjønneland, Anne ; Saber, Anne Thoustrup ; Wallin, Håkan ; Jensen, Majken Karoline ; Schmidt, Erik Berg ; Andersen, Pall Skytt ; Overvad, Kim. / PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes. I: BMC Medical Genetics. 2009 ; Bind 10.
    @article{4969b8f0f9f611de89af000ea68e967b,
    title = "PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes",
    abstract = "Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPAR gamma 2 Pro(12)Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPAR gamma activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine. Methods: A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals.Results: Homozygous male variant allele carriers of PPAR gamma 2 Pro(12)Ala were at higher risk of ACS (HR = 2.12, 95{\%} CI: 1.00-4.48) than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5-38.7) compared to homozygous common allele carriers (p for interaction < 0.0001). Overall, the association was only observed among homozygous variant allele carriers. Thus, all the observed associations were obtained in subgroups including small numbers of cases. It is therefore possible that the observed associations were due to chance.Conclusion: In the present study, there were no consistent associations between PPAR gamma Pro(12)Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.",
    author = "Ulla Vogel and Stine Segel and Claus Dethlefsen and Anne Tj{\o}nneland and Saber, {Anne Thoustrup} and H{\aa}kan Wallin and Jensen, {Majken Karoline} and Schmidt, {Erik Berg} and Andersen, {Pall Skytt} and Kim Overvad",
    year = "2009",
    doi = "10.1186/1471-2350-10-52",
    language = "English",
    volume = "10",
    journal = "B M C Medical Genetics",
    issn = "1471-2350",
    publisher = "BioMed Central Ltd.",

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    Vogel, U, Segel, S, Dethlefsen, C, Tjønneland, A, Saber, AT, Wallin, H, Jensen, MK, Schmidt, EB, Andersen, PS & Overvad, K 2009, 'PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes', BMC Medical Genetics, bind 10. https://doi.org/10.1186/1471-2350-10-52

    PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes. / Vogel, Ulla; Segel, Stine; Dethlefsen, Claus; Tjønneland, Anne; Saber, Anne Thoustrup; Wallin, Håkan; Jensen, Majken Karoline; Schmidt, Erik Berg; Andersen, Pall Skytt; Overvad, Kim.

    I: BMC Medical Genetics, Bind 10, 2009.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - PPAR gamma Pro(12)Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

    AU - Vogel, Ulla

    AU - Segel, Stine

    AU - Dethlefsen, Claus

    AU - Tjønneland, Anne

    AU - Saber, Anne Thoustrup

    AU - Wallin, Håkan

    AU - Jensen, Majken Karoline

    AU - Schmidt, Erik Berg

    AU - Andersen, Pall Skytt

    AU - Overvad, Kim

    PY - 2009

    Y1 - 2009

    N2 - Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPAR gamma 2 Pro(12)Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPAR gamma activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine. Methods: A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals.Results: Homozygous male variant allele carriers of PPAR gamma 2 Pro(12)Ala were at higher risk of ACS (HR = 2.12, 95% CI: 1.00-4.48) than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5-38.7) compared to homozygous common allele carriers (p for interaction < 0.0001). Overall, the association was only observed among homozygous variant allele carriers. Thus, all the observed associations were obtained in subgroups including small numbers of cases. It is therefore possible that the observed associations were due to chance.Conclusion: In the present study, there were no consistent associations between PPAR gamma Pro(12)Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.

    AB - Background: Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPAR gamma 2 Pro(12)Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPAR gamma activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine. Methods: A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals.Results: Homozygous male variant allele carriers of PPAR gamma 2 Pro(12)Ala were at higher risk of ACS (HR = 2.12, 95% CI: 1.00-4.48) than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5-38.7) compared to homozygous common allele carriers (p for interaction < 0.0001). Overall, the association was only observed among homozygous variant allele carriers. Thus, all the observed associations were obtained in subgroups including small numbers of cases. It is therefore possible that the observed associations were due to chance.Conclusion: In the present study, there were no consistent associations between PPAR gamma Pro(12)Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.

    U2 - 10.1186/1471-2350-10-52

    DO - 10.1186/1471-2350-10-52

    M3 - Journal article

    VL - 10

    JO - B M C Medical Genetics

    JF - B M C Medical Genetics

    SN - 1471-2350

    ER -