Pollex Rebecca L, Mamakeesick Mary, Zinman Bernard, Harris Stewart B, Hegele Robert A, Hanley Anthony J G
Robarts Research Institute, London, Ontario, Canada N6A 5K8.
J Diabetes Complications. 2007 May-Jun;21(3):166-71. doi: 10.1016/j.jdiacomp.2006.02.006.
One putative determinant of diabetic nephropathy is the Pro12Ala (P12A) polymorphism in the gene encoding peroxisome proliferator-activated receptor gamma (PPARgamma). Previous research has found a "protective" role for the A12 allele in association with type 2 diabetes, atherosclerosis, and measures of kidney damage. The objective of this study was to investigate a possible role for the P12A PPARgamma gene polymorphism with diabetic nephropathy in an isolated aboriginal Canadian population at high risk for renal disease.
The P12A PPARgamma gene polymorphism was genotyped in 159 subjects (62 men and 97 women) of Oji-Cree descent. Participants were selected from a communitywide survey, which included diabetic nephropathy assessment by albumin/creatinine (A/C) ratio measurement. Genetic associations were tested by multivariate regression analysis, using a forward stepwise modeling approach.
PPARgamma A12 allele carriers had reduced prevalence of microalbuminuria with a approximately 1.5-fold reduction in A/C ratio. Both PPARG P12A genotype [odds ratio (OR)=0.25, 95% confidence interval (95% CI)=0.076-0.85, P=.026] and systolic blood pressure (OR=1.69, 95% CI=1.15-2.48, P=.0075) were associated with microalbuminuria.
The genetic influence of PPARG P12A genotype is modest and is overshadowed by duration of diabetes and systolic blood pressure as the major risk factors for diabetic nephropathy in the Oji-Cree population. The observed genetic association with diabetic nephropathy, however, confirms earlier findings, highlighting the importance of this polymorphism.
糖尿病肾病的一个假定决定因素是过氧化物酶体增殖物激活受体γ（PPARγ）编码基因中的Pro12Ala（P12A）多态性。先前的研究发现A12等位基因在2型糖尿病、动脉粥样硬化及肾脏损伤指标方面具有“保护”作用。本研究的目的是在一个孤立的、患肾病风险高的加拿大原住民人群中，调查P12A PPARγ基因多态性与糖尿病肾病之间可能存在的关系。
对159名奥吉 - 克里族后裔受试者（62名男性和97名女性）的P12A PPARγ基因多态性进行基因分型。参与者选自一项全社区调查，该调查包括通过白蛋白/肌酐（A/C）比值测量进行糖尿病肾病评估。采用向前逐步建模方法，通过多变量回归分析检验基因关联性。
PPARγ A12等位基因携带者微量白蛋白尿的患病率降低，A/C比值降低约1.5倍。PPARG P12A基因型[比值比（OR）=0.25，95%置信区间（95%CI）=0.076 - 0.85，P = 0.026]和收缩压（OR = 1.69，95%CI = 1.15 - 2.48，P = 0.0075）均与微量白蛋白尿相关。
在奥吉 - 克里族人群中，PPARG P12A基因型的遗传影响较小，与糖尿病病程和收缩压相比显得微不足道，而糖尿病病程和收缩压是糖尿病肾病的主要危险因素。然而，观察到的与糖尿病肾病的基因关联性证实了早期研究结果，突出了这种多态性的重要性。
