PPARγ2基因P12A多态性与上海地区汉族人群2型糖尿病肾病

Peroxisome proliferator activated receptor γ2 gene P12A polymorphism and type 2 diabetic nephropathy in Han population in Shanghai

目的探讨过氧化物酶体增殖物激活受体γ2(PPARγ2)基因Pro12Ala(P12A)多态性与上海地区汉族人群2型糖尿病(T2DM)肾病的相关性。方法上海地区汉族人群中无血缘关系的2型糖尿病患者259例,根据24 h尿白蛋白排泄率(AER)分为糖尿病无肾病组(DN-0组,n=94)和糖尿病肾病组(DN组,n=165)。DN组进一步分为微量蛋白尿肾病组(DN-1组,n=95)和显性蛋白尿肾病组(DN-2组,n=70)。应用PCR直接测序法,检测各组PPARγ2基因外显子B的P12A多态性基因型,比较组间基因型、等位基因频率及临床变量间的差异。结果检测到P12P12和P12A12二种基因型,未检测到A12A12。T2DM各亚组PPARγ2基因型频率分布均符合Hardy-Weinberg遗传平衡定律。与DN-0组相比,DN-1组和DN-2组P12A12基因型及A12等位基因频率均呈下降趋势,但无统计学差异(P>0.05)。DN组P12A12基因型及A12等位基因频率均显著低于DN-0组,其中基因型为9.1%vs18.1%(P=0.034,OR=0.453),等位基因为4.5%vs9.0%(P=0.041,OR=0.479)。结论研究结果提示PPARγ2基因P12A多态性与上海地区汉族人群T2DM肾病发病相关,A12等位基因可能有防止T2DM肾病进展的作用。

Objective To explore the relationship between P12A polymorphism of peroxisome proliferator activated receptorγ2（PPARγ2）gene and type 2 diabetic nephropathy in Shanghai. Methods A total of 259 unrelated type 2 diabetic patients of Chinese in Shanghai were selected for the study.According to 24 h urinary albumin excretion rate（AER）,patients with type 2 diabetes were divided into two groups： non-diabetic nephropathy group,i.e.,DN-0 group（n=94） and diabetic nephropathy group,i.e.,DN group（n=165）.DN group was further subdivided into microalbu-minuria nephropathy group（DN-1 group,n=95） and overt proteinuria nephropathy group（DN-2 group,n=70）.PCR-direct sequencing was used to detect genotypes of P12A polymorphism in exon 2 of PPARγ2 gene for type B diabetic patients with or without nephropathy.Genotypic and allelic frequencies and clinical characteristics were compared among the groups.Results Two genetypes were detected,i.e.,P12P12 and P12A12,but no A12A12 was detected.The genotypic distribution of PPARγ2P12A in each group was in Hardy-Weinberg equilibrium law.In comparison with DN-0 group,frequencies of P12A12 genotype and A12 allele in DN-1 and DN-2 group were decreased（P〉0.05）.Frequencies of P12A12 genotype and A12 allele in DN group were significantly decreased respectively,when compared with DN-0 group（for P12A12 genotype,9.1% vs 18.1%,P=0.034,OR=0.453;for A12 allele,4.5% vs 9.0%,P=0.041,OR=0.479）. Conclusion The observations suggest that P12A polymorphism of PPARγ2 gene is associated with Chinese type 2 diabetic nephropathy,and A12 allele may protect the development of diabetic nephropathy in type 2 diabetic patients of Chinese.