Matrix metalloproteinase-2 functional promoter polymorphism G1575A is associated with elevated circulatory MMP-2 levels and increased risk of cardiovascular disease in systemic lupus erythematosus patients.
Matrix metalloproteinase-2 (MMP-2) is a zinc dependent endonuclease that degrades type IV collagen, the major structural component of basement membranes. MMP-2 functional promoter polymorphism G1575A affects circulating level of MMP-2 and may be considered an important genetic determinant of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) patients. In this study, association between MMP-2 1575A allele with serum MMP-2, neopterin and lipid-lipoprotein levels and with SLE and developing CVD was investigated. The present case-control study consisted of 109 SLE patients with and without CVD (mean age, 35.6 years) and 101 gender- and age-matched, unrelated, healthy controls (mean age, 37.1 years) from the population in the west of Iran. MMP-2 1575G/A polymorphism was detected by polymerase chain reaction (restriction fragment length polymorphism) PCR-RFLP, serum MMP-2, neopterin and lipid levels were determined by enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC) and enzyme assay, respectively. The presence of MMP-2 G1575A allele was found to be associated with SLE and developed CVD (OR = 1.78, p = 0.029 and OR = 3.43, p = 0.025, respectively). The SLE patients with MMP-2 A (G/A + A/A) allele had higher MMP-2 activity (301 ± 166 vs. 194 ± 35.5, p = 0.002), neopterin (29.4 ± 39.4 vs. 7.3 ± 4.6, p = 0.005), LDL-C (120 ± 25.7 vs. 87 ± 39.3, p = 0.045) and lower HDL-C (39.6 ± 11 vs. 45.9 ± 11.8, p = 0.031) levels than the control subjects. There was a significantly positive correlation between MMP-2 level with neopterin, total cholesterol and TG levels and negative correlation with HDL-C level in SLE patients with CVD. MMP-2 G1575A allele may be a risk factor for SLE. The carriers of this allele have high levels of MMP-2, neopterin, total cholesterol and TG and lower levels of HDL, thus, they are more likely to develop heart disease.
Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Iran.
F
F
Bahrehmand
A
A
Vaisi-Raygani
A
A
Kiani
Z
Z
Rahimi
H
H
Tavilani
S J
SJ
Navabi
E
E
Shakiba
N
N
Hassanzadeh
T
T
Pourmotabbed
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D007492:Iran; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications / Q000235:genetics*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
D014280:Triglycerides; D019798:Neopterin; D002784:Cholesterol; D020778:Matrix Metalloproteinase 2