Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes

A. S. Doney, B. Fischer, J. E. Cecil, K. Boylan, Fiona Elizabeth Anne McGuigan, S Ralston, A. D. Morris, C. N. Palmer

    Research output: Contribution to journalArticle

    101 Citations (Scopus)

    Abstract

    Aims/hypothesis. The Pro12Ala polymorphism of peroxisome proliferator-activated receptor (PPAR)gamma has been consistently associated with Type 2 diabetes. The rare Ala12 variant is estimated to reduce the risk of developing Type 2 diabetes by 20 percent. This variant is in linkage disequilibrium with another common variant, T1431. Both have opposing associations with body weight. We therefore examined the association of specific haplotypes marked by these two variants with susceptibility to Type 2 diabetes.

    Methods. We determined the PPARG genotype of a large Scottish cohort of Type 2 diabetic patients (n=1997) and compared allele frequencies with a cohort of local children (n=2444) and a middle-aged, population-based cohort from Scotland (n=1061).

    Results. Frequency of the Ala12 allele was slightly lower in the Type 2 diabetic cohort than in the children [odds ratio (OR)=0.91, p=0.1]. In contrast, the Ala12 variant was under-represented in the Type 2 diabetic population when compared with similarly aged non-diabetic adults (OR=0.74, p=0.0006). When the Ala12 variant was on a haplotype not bearing the 1431T variant, it conferred greater protection (OR=0.66, p=0.003). However, when it was present in haplotypes containing the 1431T variant (70% of Ala12 carriers), this protection was absent (OR=0.99, p=0.94).

    Conclusions/interpretation. We replicated the finding that the Ala12 variant of PPARgamma affords protection from Type 2 diabetes, and suggest that this protection is modulated by additional common variation at the PPARG locus.

    Original languageEnglish
    Pages (from-to)555-558
    Number of pages3
    JournalDiabetologia
    Volume47
    Issue number3
    DOIs
    Publication statusPublished - 2004

    Keywords

    • Type 2 diabetes
    • susceptibility
    • haplotype
    • polymorphism
    • peroxisome proliferator
    • INSULIN SENSITIVITY
    • GENE
    • HYPERTENSION
    • POLYMORPHISM
    • SUBSTITUTION

    Cite this

    Doney, A. S., Fischer, B., Cecil, J. E., Boylan, K., McGuigan, F. E. A., Ralston, S., ... Palmer, C. N. (2004). Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes. Diabetologia, 47(3), 555-558. https://doi.org/10.1007/s00125-003-1323-1

    Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes. / Doney, A. S.; Fischer, B.; Cecil, J. E.; Boylan, K.; McGuigan, Fiona Elizabeth Anne; Ralston, S; Morris, A. D.; Palmer, C. N.

    In: Diabetologia, Vol. 47, No. 3, 2004, p. 555-558.

    Research output: Contribution to journalArticle

    Doney, AS, Fischer, B, Cecil, JE, Boylan, K, McGuigan, FEA, Ralston, S, Morris, AD & Palmer, CN 2004, 'Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes', Diabetologia, vol. 47, no. 3, pp. 555-558. https://doi.org/10.1007/s00125-003-1323-1
    Doney, A. S. ; Fischer, B. ; Cecil, J. E. ; Boylan, K. ; McGuigan, Fiona Elizabeth Anne ; Ralston, S ; Morris, A. D. ; Palmer, C. N. / Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes. In: Diabetologia. 2004 ; Vol. 47, No. 3. pp. 555-558.
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    abstract = "Aims/hypothesis. The Pro12Ala polymorphism of peroxisome proliferator-activated receptor (PPAR)gamma has been consistently associated with Type 2 diabetes. The rare Ala12 variant is estimated to reduce the risk of developing Type 2 diabetes by 20 percent. This variant is in linkage disequilibrium with another common variant, T1431. Both have opposing associations with body weight. We therefore examined the association of specific haplotypes marked by these two variants with susceptibility to Type 2 diabetes.Methods. We determined the PPARG genotype of a large Scottish cohort of Type 2 diabetic patients (n=1997) and compared allele frequencies with a cohort of local children (n=2444) and a middle-aged, population-based cohort from Scotland (n=1061).Results. Frequency of the Ala12 allele was slightly lower in the Type 2 diabetic cohort than in the children [odds ratio (OR)=0.91, p=0.1]. In contrast, the Ala12 variant was under-represented in the Type 2 diabetic population when compared with similarly aged non-diabetic adults (OR=0.74, p=0.0006). When the Ala12 variant was on a haplotype not bearing the 1431T variant, it conferred greater protection (OR=0.66, p=0.003). However, when it was present in haplotypes containing the 1431T variant (70{\%} of Ala12 carriers), this protection was absent (OR=0.99, p=0.94).Conclusions/interpretation. We replicated the finding that the Ala12 variant of PPARgamma affords protection from Type 2 diabetes, and suggest that this protection is modulated by additional common variation at the PPARG locus.",
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    TY - JOUR

    T1 - Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes

    AU - Doney, A. S.

    AU - Fischer, B.

    AU - Cecil, J. E.

    AU - Boylan, K.

    AU - McGuigan, Fiona Elizabeth Anne

    AU - Ralston, S

    AU - Morris, A. D.

    AU - Palmer, C. N.

    PY - 2004

    Y1 - 2004

    N2 - Aims/hypothesis. The Pro12Ala polymorphism of peroxisome proliferator-activated receptor (PPAR)gamma has been consistently associated with Type 2 diabetes. The rare Ala12 variant is estimated to reduce the risk of developing Type 2 diabetes by 20 percent. This variant is in linkage disequilibrium with another common variant, T1431. Both have opposing associations with body weight. We therefore examined the association of specific haplotypes marked by these two variants with susceptibility to Type 2 diabetes.Methods. We determined the PPARG genotype of a large Scottish cohort of Type 2 diabetic patients (n=1997) and compared allele frequencies with a cohort of local children (n=2444) and a middle-aged, population-based cohort from Scotland (n=1061).Results. Frequency of the Ala12 allele was slightly lower in the Type 2 diabetic cohort than in the children [odds ratio (OR)=0.91, p=0.1]. In contrast, the Ala12 variant was under-represented in the Type 2 diabetic population when compared with similarly aged non-diabetic adults (OR=0.74, p=0.0006). When the Ala12 variant was on a haplotype not bearing the 1431T variant, it conferred greater protection (OR=0.66, p=0.003). However, when it was present in haplotypes containing the 1431T variant (70% of Ala12 carriers), this protection was absent (OR=0.99, p=0.94).Conclusions/interpretation. We replicated the finding that the Ala12 variant of PPARgamma affords protection from Type 2 diabetes, and suggest that this protection is modulated by additional common variation at the PPARG locus.

    AB - Aims/hypothesis. The Pro12Ala polymorphism of peroxisome proliferator-activated receptor (PPAR)gamma has been consistently associated with Type 2 diabetes. The rare Ala12 variant is estimated to reduce the risk of developing Type 2 diabetes by 20 percent. This variant is in linkage disequilibrium with another common variant, T1431. Both have opposing associations with body weight. We therefore examined the association of specific haplotypes marked by these two variants with susceptibility to Type 2 diabetes.Methods. We determined the PPARG genotype of a large Scottish cohort of Type 2 diabetic patients (n=1997) and compared allele frequencies with a cohort of local children (n=2444) and a middle-aged, population-based cohort from Scotland (n=1061).Results. Frequency of the Ala12 allele was slightly lower in the Type 2 diabetic cohort than in the children [odds ratio (OR)=0.91, p=0.1]. In contrast, the Ala12 variant was under-represented in the Type 2 diabetic population when compared with similarly aged non-diabetic adults (OR=0.74, p=0.0006). When the Ala12 variant was on a haplotype not bearing the 1431T variant, it conferred greater protection (OR=0.66, p=0.003). However, when it was present in haplotypes containing the 1431T variant (70% of Ala12 carriers), this protection was absent (OR=0.99, p=0.94).Conclusions/interpretation. We replicated the finding that the Ala12 variant of PPARgamma affords protection from Type 2 diabetes, and suggest that this protection is modulated by additional common variation at the PPARG locus.

    KW - Type 2 diabetes

    KW - susceptibility

    KW - haplotype

    KW - polymorphism

    KW - peroxisome proliferator

    KW - INSULIN SENSITIVITY

    KW - GENE

    KW - HYPERTENSION

    KW - POLYMORPHISM

    KW - SUBSTITUTION

    U2 - 10.1007/s00125-003-1323-1

    DO - 10.1007/s00125-003-1323-1

    M3 - Article

    VL - 47

    SP - 555

    EP - 558

    JO - Diabetologia

    JF - Diabetologia

    SN - 0012-186X

    IS - 3

    ER -