제2형 당뇨병 환자에서 허혈성 뇌졸중 발생과 Interleukin-1 Receptor Antagonist 및 Peroxisome Proliferator-Activated Receptor-γ2 유전자 다형성과의 관계
The Association of Interleukin-1 Receptor Antagonist and Peroxisome Proliferator-Activated Receptor-γ2 Pro12Ala Polymorphism with Ischemic Stroke in Type 2 Diabetes Mellitus Patients
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Abstract
Objective : It has been reported that two-repeats (IL1RN*2) of interleukin-1 receptor antagonist (IL-1Ra) gene is associated with ischemic stroke, and that Ala allele of the common Pro12Ala polymorphism in PPAR-γ2 isoform is associated with reduced risk for type 2 DM and its complications. The aim of the present study is to assess the association of IL-1Ra and PPAR-γ2 Pro12Ala polymorphism with the presence of ischemic stroke in the case of diabetic and non-diabetic patients.Methods : Genomic DNA was obtained from 373 healthy subjects, 157 DM subjects without ischemic stroke (known DM duration ≥10 years) and 302 ischemic stroke patients (including with DM). IL-1Ra polymorphism was analyzed by polymerase chain reaction (PCR), and PPAR-γ2 polymorphism by restriction fragment length polymorphism after PCR.Results : IL1RN*1/IL1RN*2 genotype was associated with significantly increased risk for DM (OR=2.86, P = 0.0008) and ischemic stroke (OR=2.74, P = 0.0016). Pro/Ala genotype was associated with the reduced risk for DM (OR=0.53, P = 0.0491) and ischemic stroke (OR=0.38, P = 0.0039). They were also associated with the reduced risk for ischemic stroke in the DM patients compared with DM without ischemic stroke (OR=0.25, P = 0.0321). Conclusions : IL1RN*2 allele could be an accelerating factor, not a predictive marker for ischemic stroke in type 2 DM. The Pro/Ala genotype of PPAR-γ2 Pro12Ala polymorphism may be associated with reduced risk for ischemic stroke with type 2 DM. Therefore it could be a useful predictive marker for ischemic stroke in Korean type 2 DM.
참고문헌 (19)
- "The common PPARγPro12Ala polymorphism is associated with decreased risk of type 2 diabetes", 26(1), pp.76~80 (2000)
- "The human peroxisome proliferator- activated receptorγ2 (PPARγ2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes", 52(12), pp.3010~3013 (2003)
- "Role of IL-1α and IL-1β in ischemic brain damage", 21(15), pp.5528~5534 (2001)
- "Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism", 99(2), pp.303~310 (1995)
- "The human peroxisome proliferator- activated receptorγ2 (PPARγ2) Pro12Ala polymorphism is associated with decreased risk of diabetic nephropathy in patients with type 2 diabetes", 52(12), pp.3010~3013 (2003)
- "Activated inflammatory cells are associated with plaque rupture in carotid artery stenosis", 122(4), pp.757~763 (1997)
- "Biologic basis for interleukin-1 in disease", 87(6), pp.2095~2108 (1996)
- "Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat", pp.403~4 (1993)
- Tountas NA,, "Functional and ethnic association of allele 2 of the interleukin-1 receptor antagonist gene in ulcerative colitis", 117(4), pp.806~813 (1999)
- Marculescu R,, "Interleukin-1 receptor antagonist genotype is associated with coronary atherosclerosis in patients with type 2 diabetes", 51(12), pp.3582~3585 (2002)
- Lee BC,, "Susceptibility for ischemic stroke is associated with polymorphisms of the interleukin-1 receptor antagonist and tumor necrosis factor- genes, but not the interleukin-1 gene", 357, pp.33~36 (2004)
- Issemann I, "Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators", pp.645~50 (1990)
- Werman A,, "Ligand- independent activation domain in the N terminus of peroxisome proliferator-activated receptor γ (PPARγ). Differential activity of PPARgamma1 and -2 isoforms and influence of insulin", 272(32), pp.20230~20235 (1997)
- Vidal-Puig AJ,, "Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids", 99(10), pp.2416~2422 (1997)
- Lehmann JM,, "An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptorγ (PPARγ)", 270(22), pp.12953~12956 (1995)
- Yen CJ,, "Molecular scanning of the human peroxisome proliferator activated receptor γ (hPPARγ) gene in diabetic Caucasians: identification of a Pro12Ala PPARγ2 missense mutation", 241(2), pp.270~274 (1997)
- Jacob S,, "The PPARγ2 polymorphism pro12Ala is associated with better insulin sensitivity in the offspring of type 2 diabetic patients", 32(10), pp.413~416 (2000)
- Ringel J,, "Pro12Ala missense mutation of the peroxisome proliferator activated receptor γ and diabetes mellitus", 254(2), pp.450~453 (1999)
- Ostgren CJ,, "Peroxisome proliferator-activated receptor-γPro12Ala polymorphism and the association with blood pressure in type 2 diabetes: skaraborg hypertension and diabetes project", 21(9), pp.1657~1662 (2003)
