Impact of ENPP1 and MMP3 gene polymorphisms on aortic calcification in patients with type 2 diabetes in a Korean population.
OBJECTIVE
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.
Lee
Jung-Eun
JE
Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea.
Choi
Yeon-Kyung
YK
Seo
Hyun-Ae
HA
Jeon
Jae-Han
JH
Jeong
Ji-Yun
JY
Moon
Seong-Su
SS
Kim
Jung-Guk
JG
Kim
Bo-Wan
BW
Kim
Su-Won
SW
Min Yoo
Kim
Joon-Young
JY
Lee
In-Kyu
IK
D000328:Adult; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D001018:Aortic Diseases / Q000097:blood / Q000150:complications / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001823:Body Composition; D002114:Calcinosis / Q000097:blood / Q000150:complications / Q000235:genetics*; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics*; D004032:Diet; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics*; D012044:Regression Analysis; D056910:Republic of Korea
D053244:Osteoprotegerin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D011755:Pyrophosphatases