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

被引:109
作者
Doney, ASF
Fischer, B
Cecil, JE
Boylan, K
McGuigan, FE
Ralston, SH
Morris, AD
Palmer, CNA [1 ]
机构
[1] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland
[2] Univ Dundee, Ninewells Hosp & Med Sch, Dept Med, Dundee DD1 9SY, Scotland
[3] Univ Dundee, Ninewells Hosp & Med Sch, Dept Clin Pharmacol, Dundee DD1 9SY, Scotland
[4] Univ Dundee, Dept Psychol, Dundee DD1 4HN, Scotland
[5] Univ Aberdeen, Sch Med, Inst Med Sci, Aberdeen AB9 2ZD, Scotland
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
Type; 2; diabetes; susceptibility; haplotype; polymorphism; peroxisome proliferator;
D O I
10.1007/s00125-003-1323-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:555 / 558
页数:4
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