Summary
The aim of this investigation was to determine whether a PPARγ2 Pro12Ala polymorphism was associated with insulin resistance, β-cell function and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes (HbAC1<6.0) were investigated, including 132 hypertensive diabetic (HTD) subjects, 157 normotensive diabetic (NTD) subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test (OGTT). Biochemical measurements (high-density lipoprotein (HDL) and low-density lipoprotein-cholesterol (LDL), triglycerides) and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group (3.03%) than in the non-hypertension group (5.7%) (P<0.05) after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level (P=0.0127), and better glucose tolerance 60 min after oral glucose (P=0.0361). Moreover, plasma insulin concentrations at 60 min was lower than those without A variant (P=0.0275), and both hypertensive Ala/Pro in HOMA-β (P=0.0455) and AUC for insulin (P=0.0473) were higher, and HOMA-IR was lower (P=0.0375) as compared with hypertensive Pro/Pro subjects. No association was observed between Pro12Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPAR γ2 on glucose homeostasis and insulin resistance.
Similar content being viewed by others
References
Florez J C, Hirschhorn J, Altshuler D. The inherited basis of diabetes mellitus: implications for the genetic analysis of complex traits. Annu Rev Genomics Hum Genet, 2003, 4: 257
Rosmond R, Chagnon M, Bouchard C. The Pro12Ala PPARgamma2 gene missense mutation is associated with obesity and insulin resistance in Swedish middle-aged men. Diabetes Metab Res Rev, 2003, 19: 159
Hara K, Okada T, Tobe Ket al. The Prol2Ala Polymorphism in PPAR 2 May Confer Resistance to Type 2 Diabetes. Biochem Biophys Res Commun, 2000, 271: 212
Wang C X, Zhai F Y, Chi Y Jet al. Association of Pro12Ala mutation in peroxisome proliferator activated receptorγ2 with obesity and diabetes in Chinese population. J Hyg Res, 2004, 33(3): 317
Amori Y, Masugi J, Nishino Net al. Role of peroxisome proliferator-activated receptor-gamma in maintenance of the characteristics of mature 3T3-L1 adipocytes Diabetes, 2002, 51: 20456
Kim H I, Ahn Y H. Role of peroxisome proliferator activated receptor-γin the glucosesensing apparatus of liver and β-cells Diabetes, 2004, 53: 60
Masugi J, Tamori Y, Mori Het al. Inhibitory effect of a proline-toalanine substitution at codon 12 of peroxisome proliferator activated receptor-gamma 2 on thiazolidinedione-induced adipogenesis. Biochem Biophys Res Commun, 2000, 268: 178
Chuang L M, Hsiung C A, Chen Y Det al. Sibling-based association study of the PPARγ2 Pro12Ala polymorphism and metabolic variables in Chinese and Japanese hypertension families: a SAPPHIRe study. J Mol Med, 2001, 79: 656
Yliharsila H, Eriksson J G, Forsen Tet al. Interactions between peroxisome proliferator-activated receptor-γ2 gene polymorphisms and size at birth on blood pressure and the use of antihypertensive medication. J Hypertens, 2004, 22: 1283
Author information
Authors and Affiliations
Additional information
ZHANG Aiping, female, born in 1967. Associate Professor
Rights and permissions
About this article
Cite this article
Aiping, Z., Muxun, Z., Jianhua, Z. et al. The influence of the Pro12Ala mutation of PPARγ2 receptor gene on β-cells restoration and insulin resistance in type 2 diabetes with hypertension. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 25, 648–650 (2005). https://doi.org/10.1007/BF02896160
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02896160