Matrix metalloproteinase-2 promoter variability in psoriasis.
The expression of matrix metalloproteinase-2 was observed to be significantly upregulated in psoriasis. The aim of this study was to associate the DNA polymorphic variants in MMP-2 promoter gene with psoriasis and/or with psoriasis phenotypes related to psoriasis and comorbid heredity. In the total of 582 Czech Caucasian individuals (386 patients with psoriasis and 196 controls of similar age and sex distribution without personal or family history of chronic disease of the skin), four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) were detected by PCR methods. A significant association of GG genotype of -790 MMP-2 polymorphism with psoriasis was observed (Pcorr = 0.04). Although no significant case-control differences in frequency of associated GG(-1575)CC(-1306)TT(-790) MMP-2 promoter genotype were observed, the genotype was found to be significantly less frequent in patients with family history of psoriasis (close as well as distant), family history of diabetes and personal history of allergy (2/11 vs. 55/32, odds ratio (OR) for GGCCTT 0.11, 95% confidential interval 0.02-0.50, Pcorr = 0.01). The significant difference between psoriatic patients with positive anamnestic data on diabetes, psoriasis and allergy compared with psoriatic patients that have only positive family history of diabetes was also observed (2/11 vs. 38/31, P = 0.009, Pcorr = 0.04; OR 0.15, 95% CI = 0.03-0.72 for psoriatic patients with GGCCTT genotype and family history of psoriasis, diabetes and personal history of allergy). To conclude, the associated GGCCTT genotype in the promoter of MMP-2 gene was less frequent in patients with positive family history of psoriasis, diabetes and personal history of allergy compared with psoriatic patients without them (2/11 vs. 68/57, P = 0.007, Pcorr = 0.04; OR = 0.15, 95% CI = 0.03-0.72 for psoriatic patients with family history of psoriasis and diabetes and with allergy). Based on our results, we suggest that the MMP-2 located in the psoriasis susceptibility region on 16q (psoriasis susceptibility 8, PSORS8) should be considered as a gene modulator of psoriasis in specific subgroups of patients. In the future, similar genetic characteristics could contribute to the data assembly of genetic predisposition to psoriasis and could lead to therapy improvement based on time-proved individual pharmacogenetic aspects detected in psoriasis patients.
1st Department of Dermatology, St. Ann's Faculty Hospital, Masaryk University Brno, Pekarská 53, Brno 656 91, Czech Republic. vladimir.vasku@fnusa.cz
Vladimir
V
Vasku
Julie
J
Bienertova Vasku
Veronika
V
Slonková
Katerina
K
Kanková
Anna
A
Vasku
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002885:Chromosomes, Human, Pair 16; D018153:Czech Republic; D003920:Diabetes Mellitus / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D010375:Pedigree; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology*
D020778:Matrix Metalloproteinase 2