Paraoxonase 1 192Gln/Arg polymorphism is associated with the risk of microangiopathy in Type 2 diabetes mellitus

Mitsuru Murata, T. Maruyama, Y. Suzuki, T. Saruta, Y. Ikeda

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Aims: To investigate possible associations between diabetic microangiopathy and genetic polymorphisms in factors relevant to arterial thrombosis. Methods: We conducted a case-control study on a total of 280 patients with Type 2 diabetes, comparing those without retinopathy or nephropathy (n = 92) and those with microangiopathies (n = 188), for the association of polymorphisms in four candidate genes, paraoxonase 1 (PON1), plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibα. Results: There were no differences between the two study groups in gender distribution, age at diagnosis of diabetes (47.9 ± 8.4 and 49.0 ± 11.4 years, respectively), or duration of diabetes (14.9 ± 4.5 and 14.5 ± 8.4 years, respectively). Among the gene polymorphisms tested, the 192Gln/Arg polymorphism of PON1 was associated with the prevalence of retinopathy [odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.42-6.89, P = 0.0046, Gin/Gin vs. Gln/Arg and Arg/Arg]. This polymorphism was also associated with nephropathy (OR = 3.01, 95% CI = 1.30-6.98, P = 0.0103). There were no differences between the three PON1 genotypes (Gln/Gln, Gln/Arg, and Arg/Arg) with regard to the present disease status. Logistic regression analysis for the adjustment of other risk factors revealed that genotypes with PON1 192Arg were an independent predictor of retinopathy. No associations were found between microangiopathies and the other polymorphisms evaluated (plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibα). Conclusions: This study suggests that the presence of the 192Arg-allele in the PON1 gene is a genetic risk factor for microangiopathy in Type 2 diabetes mellitus.

Original languageEnglish
Pages (from-to)837-844
Number of pages8
JournalDiabetic Medicine
Volume21
Issue number8
DOIs
Publication statusPublished - 2004 Aug

Fingerprint

Aryldialkylphosphatase
Type 2 Diabetes Mellitus
Platelet Membrane Glycoproteins
Plasminogen Activator Inhibitor 1
Fibrinogen
Odds Ratio
Genotype
Platelet Glycoprotein GPIb-IX Complex
Confidence Intervals
Genes
Diabetic Angiopathies
Age Distribution
Genetic Polymorphisms
Case-Control Studies
Thrombosis
Logistic Models
Alleles
Regression Analysis

Keywords

  • Genetics
  • Microangiopathy
  • Paraoxonase 1
  • Polymorphism
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Paraoxonase 1 192Gln/Arg polymorphism is associated with the risk of microangiopathy in Type 2 diabetes mellitus. / Murata, Mitsuru; Maruyama, T.; Suzuki, Y.; Saruta, T.; Ikeda, Y.

In: Diabetic Medicine, Vol. 21, No. 8, 08.2004, p. 837-844.

Research output: Contribution to journalArticle

Murata, Mitsuru ; Maruyama, T. ; Suzuki, Y. ; Saruta, T. ; Ikeda, Y. / Paraoxonase 1 192Gln/Arg polymorphism is associated with the risk of microangiopathy in Type 2 diabetes mellitus. In: Diabetic Medicine. 2004 ; Vol. 21, No. 8. pp. 837-844.
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abstract = "Aims: To investigate possible associations between diabetic microangiopathy and genetic polymorphisms in factors relevant to arterial thrombosis. Methods: We conducted a case-control study on a total of 280 patients with Type 2 diabetes, comparing those without retinopathy or nephropathy (n = 92) and those with microangiopathies (n = 188), for the association of polymorphisms in four candidate genes, paraoxonase 1 (PON1), plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibα. Results: There were no differences between the two study groups in gender distribution, age at diagnosis of diabetes (47.9 ± 8.4 and 49.0 ± 11.4 years, respectively), or duration of diabetes (14.9 ± 4.5 and 14.5 ± 8.4 years, respectively). Among the gene polymorphisms tested, the 192Gln/Arg polymorphism of PON1 was associated with the prevalence of retinopathy [odds ratio (OR) = 3.13, 95{\%} confidence interval (CI) = 1.42-6.89, P = 0.0046, Gin/Gin vs. Gln/Arg and Arg/Arg]. This polymorphism was also associated with nephropathy (OR = 3.01, 95{\%} CI = 1.30-6.98, P = 0.0103). There were no differences between the three PON1 genotypes (Gln/Gln, Gln/Arg, and Arg/Arg) with regard to the present disease status. Logistic regression analysis for the adjustment of other risk factors revealed that genotypes with PON1 192Arg were an independent predictor of retinopathy. No associations were found between microangiopathies and the other polymorphisms evaluated (plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibα). Conclusions: This study suggests that the presence of the 192Arg-allele in the PON1 gene is a genetic risk factor for microangiopathy in Type 2 diabetes mellitus.",
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T1 - Paraoxonase 1 192Gln/Arg polymorphism is associated with the risk of microangiopathy in Type 2 diabetes mellitus

AU - Murata, Mitsuru

AU - Maruyama, T.

AU - Suzuki, Y.

AU - Saruta, T.

AU - Ikeda, Y.

PY - 2004/8

Y1 - 2004/8

N2 - Aims: To investigate possible associations between diabetic microangiopathy and genetic polymorphisms in factors relevant to arterial thrombosis. Methods: We conducted a case-control study on a total of 280 patients with Type 2 diabetes, comparing those without retinopathy or nephropathy (n = 92) and those with microangiopathies (n = 188), for the association of polymorphisms in four candidate genes, paraoxonase 1 (PON1), plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibα. Results: There were no differences between the two study groups in gender distribution, age at diagnosis of diabetes (47.9 ± 8.4 and 49.0 ± 11.4 years, respectively), or duration of diabetes (14.9 ± 4.5 and 14.5 ± 8.4 years, respectively). Among the gene polymorphisms tested, the 192Gln/Arg polymorphism of PON1 was associated with the prevalence of retinopathy [odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.42-6.89, P = 0.0046, Gin/Gin vs. Gln/Arg and Arg/Arg]. This polymorphism was also associated with nephropathy (OR = 3.01, 95% CI = 1.30-6.98, P = 0.0103). There were no differences between the three PON1 genotypes (Gln/Gln, Gln/Arg, and Arg/Arg) with regard to the present disease status. Logistic regression analysis for the adjustment of other risk factors revealed that genotypes with PON1 192Arg were an independent predictor of retinopathy. No associations were found between microangiopathies and the other polymorphisms evaluated (plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibα). Conclusions: This study suggests that the presence of the 192Arg-allele in the PON1 gene is a genetic risk factor for microangiopathy in Type 2 diabetes mellitus.

AB - Aims: To investigate possible associations between diabetic microangiopathy and genetic polymorphisms in factors relevant to arterial thrombosis. Methods: We conducted a case-control study on a total of 280 patients with Type 2 diabetes, comparing those without retinopathy or nephropathy (n = 92) and those with microangiopathies (n = 188), for the association of polymorphisms in four candidate genes, paraoxonase 1 (PON1), plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibα. Results: There were no differences between the two study groups in gender distribution, age at diagnosis of diabetes (47.9 ± 8.4 and 49.0 ± 11.4 years, respectively), or duration of diabetes (14.9 ± 4.5 and 14.5 ± 8.4 years, respectively). Among the gene polymorphisms tested, the 192Gln/Arg polymorphism of PON1 was associated with the prevalence of retinopathy [odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.42-6.89, P = 0.0046, Gin/Gin vs. Gln/Arg and Arg/Arg]. This polymorphism was also associated with nephropathy (OR = 3.01, 95% CI = 1.30-6.98, P = 0.0103). There were no differences between the three PON1 genotypes (Gln/Gln, Gln/Arg, and Arg/Arg) with regard to the present disease status. Logistic regression analysis for the adjustment of other risk factors revealed that genotypes with PON1 192Arg were an independent predictor of retinopathy. No associations were found between microangiopathies and the other polymorphisms evaluated (plasminogen activator inhibitor-1, fibrinogen, and platelet glycoprotein Ibα). Conclusions: This study suggests that the presence of the 192Arg-allele in the PON1 gene is a genetic risk factor for microangiopathy in Type 2 diabetes mellitus.

KW - Genetics

KW - Microangiopathy

KW - Paraoxonase 1

KW - Polymorphism

KW - Type 2 diabetes

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