Impact of ENPP1 and MMP3 gene polymorphisms on aortic calcification in patients with type 2 diabetes in a Korean population

Abstract Aims We investigated whether gene polymorphisms of Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1 ) and matrix metalloproteinase 3 ( MMP3 ) are associated with increased vascular calcification in patients with type 2 diabetes (T2D) and evaluated whether serum MMP3 and osteoprot...

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Published in:Diabetes research and clinical practice 2010-04, Vol.88 (1), p.87-96
Main Authors: Lee, Jung-Eun, Choi, Yeon-Kyung, Seo, Hyun-Ae, Jeon, Jae-Han, Jeong, Ji-Yun, Moon, Seong-Su, Kim, Jung-Guk, Kim, Bo-Wan, Kim, Su-Won, Min Yoo, Kim, Joon-Young, Lee, In-Kyu
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
Analysis of Variance
Aortic Diseases - blood
Aortic Diseases - complications
Aortic Diseases - genetics
Asian Continental Ancestry Group - genetics
Body Composition
Calcification
Calcinosis - blood
Calcinosis - complications
Calcinosis - genetics
Chi-Square Distribution
Diabetes Mellitus, Type 2 - blood
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - genetics
Diet
Endocrinology & Metabolism
ENPP1
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation
Humans
Male
Matrix Metalloproteinase 3 - blood
Matrix Metalloproteinase 3 - genetics
Middle Aged
MMP3
Osteoprotegerin - blood
Phosphoric Diester Hydrolases - genetics
Polymorphism
Polymorphism, Single Nucleotide - genetics
Pyrophosphatases - genetics
Regression Analysis
Republic of Korea
Type 2 diabetes
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Summary:Abstract Aims We investigated whether gene polymorphisms of Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1 ) and matrix metalloproteinase 3 ( MMP3 ) are associated with increased vascular calcification in patients with type 2 diabetes (T2D) and evaluated whether serum MMP3 and osteoprotegerin (OPG) levels are related to calcification. Methods This study included 464 subjects: 269 patients with T2D and 195 healthy controls in South Korea. We genotyped subjects for four single nucleotide polymorphisms (SNPs): ENPP1 K121Q, ENPP1 A/G+1044TGA, MMP3 −709A>G and MMP3 −1475G>A. The presence or absence of calcifications in the aortic arch was assessed by plain chest radiography. Results The SNPs ENPP1 K121Q and MMP3 −709A>G showed significant associations with T2D ( P = 0.001 and P = 0.004). The SNP ENPP1 K121Q showed a significant association with aortic arch calcification in T2D ( P = 0.036). Serum OPG levels were significantly higher in T2D patients than in the control group ( P < 0.001). However, serum MMP3 levels were significantly lower in T2D patients than in the control group ( P < 0.001). Conclusions Our study demonstrates that the ENPP1 K121Q and MMP3 −709A>G polymorphisms are associated with T2D, and that the ENPP1 Q allele is associated with increased aortic arch calcification in a Korean population.
ISSN:0168-8227
1872-8227
DOI:10.1016/j.diabres.2010.01.002