Matrix Metalloproteinase-3 Gene Polymorphism is Associated with Coronary Artery Calcification Scores in Patients with Type 2 Diabetes Mellitus

Sang-Wook Kim; Eun Hee Cho

doi:10.4093/kdj.2009.33.2.113

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Kim and Cho: Matrix Metalloproteinase-3 Gene Polymorphism is Associated with Coronary Artery Calcification Scores in Patients with Type 2 Diabetes Mellitus

Original Article

Korean Diabetes Journal

Korean Diabetes Journal 2009; 33(2): 113-123.

Published online: 30 April 2009

DOI: https://doi.org/10.4093/kdj.2009.33.2.113

Matrix Metalloproteinase-3 Gene Polymorphism is Associated with Coronary Artery Calcification Scores in Patients with Type 2 Diabetes Mellitus

Sang-Wook Kim, Eun Hee Cho

Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.

exoplanet@kangwon.ac.kr

Received 10 March 2009 Accepted 13 April 2009

Abstract

Background

Matrix metalloproteinase-3 (MMP-3) is expressed in human coronary atherosclerotic lesions and is known to be involved in the degradation of plaque. This study examines the association of MMP-3 gene promoter 5A/6A and -709A>G polymorphisms with coronary artery calcium scores in type 2 diabetes patients.

Methods

The study comprises 140 type 2 diabetes patients aged 34~85 years, who showed no evidence of clinical cardiovascular disease before recruitment. Recruitment was based on patient's coronary artery calcium (CAC) scores and polymorphisms were identified.

Results

Multiple regression analysis showed that the CAC scores were significantly associated with age (P = 0.008), waist circumference (P = 0.03), duration of diabetes (P = 0.003) and the serum creatinine level (P = 0.012). MMP-3 5A/6A and -709A>G polymorphisms were not associated with CAC across all subjects. However, in the subgroup with a duration of diabetes over 10 years, MMP-3 -709A>G were significantly associated with CAC (P = 0.037) adjusted for age, body mass index, waist circumference and duration of diabetes.

Conclusion

Our data suggest that the CAC scores in patients with type 2 diabetes were related with age, waist circumference, duration of diabetes and higher serum creatinine levels. MMP-3 polymorphisms with -709A>G are associated with high CAC in patients with a duration of diabetes over 10 years.

Keywords: Coronary vessels, Genetic polymorphism, Matrix metalloproteinase 3, Calcinosis

Figures and Tables

Fig. 1

Box plot showing coronary artery calcification score (CACs) both in 75 subjects with the duration of diabetes less than 10 years (blank box) and in 65 subjects with the duration of diabetes more than 10 years (dashed box) according to matrix metalloproteinase-3 (MMP-3) gene -709A>G polymorphisms adjusted with age, body mass index, waist circumference and duration of diabetes (^*P value = 0.037).

Table 1

Baseline characteristics of the study subjects

^*Median and interquartile ranges of hs-CRP, microalbumin, CAC scores. BMI, body mass index; BP, blood pressure; Ca × P, calcium phosphorus product; FBS, fasting blood sugar; HbA1c, hemoglobin A1c; HDL, high density lipoprotein; hs-CRP, high sensitivty C-reactive protein; LDL, low density lipoprotein.

Table 2

Pearson correlation analysis between the coronary artery calcfication score^* and the clinical and biochemical variables

^*Log (CACs + 1). BMI, body mass index; BP, blood pressure; Ca × P, calcium phosphorus product; FBS, fasting blood sugar; HbA1c, hemoglobin A1c; HDL, high density lipoprotein; hs-CRP, high sensitivty C-reactive protein; LDL, low density lipoprotein.

Table 3

Variables predictive of determining the coronary artery calcification (CAC) score using multiple linear regression analysis with the coronary artery calcium score as dependent variable

Dependent variable: Log (CACs + 1), independent variable: age, waist circumference, duration of diabetes, serum creatinine.

Table 4

Frequencies of matrix metalloproteinase-3 (MMP-3) gene polymorphisms in the study subjects (n = 140)

^*P values of deviation from Hardy-Weinberg Equilibrium. HWE, Hardy-Weinberg Equilibrium; 5' UTR, 5' untranslated region.

Table 5

Regression analysis of coronary artery calcification score (CACs) and matrix metalloproteinase-3 (MMP-3) gene polymorphisms for all study subjects (n = 140) controlling for age, body mass index, waist circumference and duration of diabetes

^*P values of additive, dominant and recessive models.

Table 6

Regression analysis of coronary artery calcification score (CACs) and matrix metalloproteinase-3 (MMP-3) gene polymorphisms for study subjects (n = 65) with the duration of diabetes over 10 years controlling for age, body mass index, waist circumference and duration of diabetes

^*P values of additive, dominant and recessive models, in bold indicate significant association at the P < 0.05 level.

Table 7

Regression analysis of coronary artery calcification score (CACs) and matrix metalloproteinase-3 (MMP-3) haplotypes for the all study subjects (All), and for the study subjects (subgroup, n = 65) with the duration of diabetes over 10 years controlling for age, body mass index, waist circumference and duration of diabetes

^*Ht -/-, Ht +/- and Ht +/+ represent the subject without ht, heterozygote of ht, and homozygote of ht, respectively.

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