Peroxisome proliferator-activated receptor-γPro12Ala polymorphism and the association with blood pressure in type 2 diabetes:: Skaraborg Hypertension and Diabetes Project

被引:57
作者
Östgren, CJ
Lindblad, U [1 ]
Melander, O
Melander, A
Groop, L
Råstam, L
机构
[1] Malmo Univ Hosp, Dept Community Med, S-20502 Malmo, Sweden
[2] Malmo Univ Hosp, Dept Endocrinol, S-20502 Malmo, Sweden
[3] Odeshog Hlth Care Ctr, Skovde, Sweden
[4] Skaraborg Inst, Skovde, Sweden
[5] NEPI Fdn, Malmo, Sweden
[6] NEPI Fdn, Stockholm, Sweden
关键词
peroxisome proliferator-activated receptor-gamma; Pro12Ala; hypertension; blood pressure; diabetes mellitus; polymorphism; primary care; genetics; association study;
D O I
10.1097/01.hjh.0000084734.53355.0d
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Objective This study explored whether the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma (PPARgamma) is associated with blood pressure in subjects with type 2 diabetes. Design A community-based, cross-sectional observation study. Setting Primary care. Patients One hundred and ninety-two men and 192 women with type 2 diabetes who consecutively underwent annual follow-up. Main outcome measure The PPARgammaPro12Ala genotype was determined by polymerase chain reaction-based techniques. Associations between genotype and blood pressure were analysed by linear regression and expressed as differences in blood pressure (Delta) with 95% confidence interval (CI). Results The mean systolic blood pressure and the diastolic blood pressure were 160 mmHg (standard deviation = 22.8) and 84 mmHg (standard deviation = 9.6), respectively. Subjects with Pro/Ala (24%) or Ala/Ala (2%) had lower diastolic blood pressure (A = 2.8; 95% CI, 0.6-5.0) when adjusted for age and gender compared with Prol Pro subjects (74%). This association was restricted to men (Delta = 4.4; 95% CI, 1.3-7.4), who also had a borderline significant difference in systolic blood pressure (Delta = 6.9; 95% CI, -0.8 to 13.8). In men the difference in diastolic blood pressure remained after adjustment for age, body mass index, serum triglycerides, serum insulin and haemoglobin A(1c) (Delta = 4.6; 95% CI, 1.1-8.1). A subanalysis of normotensive men (n = 100) confirmed the difference associated with the Pro12Ala polymorphism in diastolic blood pressure (Delta = 5.2; 95% CI, 0.6-10.0). Conclusions The common Pro12Ala polymorphism in PPARgamma is associated with lower diastolic blood pressure in male subjects with type 2 diabetes. (C) 2003 Lippincott Williams Wilkins.
引用
收藏
页码:1657 / 1662
页数:6
相关论文
共 19 条
[1]   The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes [J].
Altshuler, D ;
Hirschhorn, JN ;
Klannemark, M ;
Lindgren, CM ;
Vohl, MC ;
Nemesh, J ;
Lane, CR ;
Schaffner, SF ;
Bolk, S ;
Brewer, C ;
Tuomi, T ;
Gaudet, D ;
Hudson, TJ ;
Daly, M ;
Groop, L ;
Lander, ES .
NATURE GENETICS, 2000, 26 (01) :76-80
[2]   Risk factor clustering in patients with hypertension and non-insulin-dependent diabetes mellitus.: The Skaraborg Hypertension Project [J].
Bog-Hansen, E ;
Lindblad, U ;
Bengtsson, K ;
Ranstam, J ;
Melander, A ;
Råstam, L .
JOURNAL OF INTERNAL MEDICINE, 1998, 243 (03) :223-232
[3]   A Pro12Ala substitution in PPARγ2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity [J].
Deeb, SS ;
Fajas, L ;
Nemoto, M ;
Pihlajamäki, J ;
Mykkänen, L ;
Kuusisto, J ;
Laakso, M ;
Fujimoto, W ;
Auwerx, J .
NATURE GENETICS, 1998, 20 (03) :284-287
[4]   The peroxisome poliferator-activated receptor-γ2 Pro12Ala variant -: Association with type 2 diabetes and trait differences [J].
Douglas, JA ;
Erdos, MR ;
Watanabe, RM ;
Braun, A ;
Johnston, CL ;
Oeth, P ;
Mohlke, KL ;
Valle, TT ;
Ehnholm, C ;
Buchanan, TA ;
Bergman, RN ;
Collins, FS ;
Boehnke, M ;
Tuomilehto, J .
DIABETES, 2001, 50 (04) :886-890
[5]   Cardiac and glycemic benefits of troglitazone treatment in NIDDM [J].
Ghazzi, MN ;
Perez, JE ;
Autonucci, TK ;
Driscoll, JH ;
Huang, SM ;
Faja, BW ;
Whitcomb, RW .
DIABETES, 1997, 46 (03) :433-439
[6]   The homeostasis model in the San Antonio Heart Study [J].
Haffner, SM ;
Miettinen, H ;
Stern, MP .
DIABETES CARE, 1997, 20 (07) :1087-1092
[7]   The Pro12Ala polymorphism in PPAR γ2 may confer resistance to type 2 diabetes [J].
Hara, K ;
Okada, T ;
Tobe, K ;
Yasuda, K ;
Mori, Y ;
Kadowaki, H ;
Hagura, R ;
Akanuma, Y ;
Kimura, S ;
Ito, C ;
Kadowaki, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 271 (01) :212-216
[8]   Effect of the peroxisome proliferator-activated receptor-γ2 Pro12Ala variant on obesity, glucose homeostasis, and blood pressure in members of familial type 2 diabetic kindreds [J].
Hasstedt, SJ ;
Ren, QF ;
Teng, K ;
Elbein, SC .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (02) :536-541
[9]   Pro12Ala substitution in the peroxisome proliferator-activated receptor-γ2 is not associated with type 2 diabetes [J].
Mancini, FP ;
Vaccaro, O ;
Sabatino, L ;
Tufano, A ;
Rivellese, AA ;
Riccardi, G ;
Colantuoni, V .
DIABETES, 1999, 48 (07) :1466-1468
[10]   Inhibitory effect of a proline-to-alanine substitution at codon 12 of peroxisome proliferator-activated receptor-γ 2 on thiazolidinedione-induced adipogenesis [J].
Masugi, J ;
Tamori, Y ;
Mori, H ;
Koike, T ;
Kasuga, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 268 (01) :178-182