Matrix metalloproteinase-2 promoter variability in psoriasis

Abstract

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.

Update on the role of plasmacytoid dendritic cells in inflammatory/autoimmune skin diseases

“…In addition, using anti‐BDCA‐2 antibody to inhibit the release of IFN‐ α by pDC prevented the development of psoriatic phenotype and inhibited the activation and expansion of pathogenetic T cells . Psoriasis susceptibility has also been associated with IRF5 , a transcription factor linked to IFN induction by pDCs, and polymorphisms in the gene encoding the receptor for advanced glycation end products (RAGE), which is known to be involved in TLR9 signalling by pDCs . However, contradictory information has been described from studies on mice.…”

The Matrix Metalloproteinase 2-<i>1575</i> gene Polymorphism is Associated with the Risk of Developing Myocardial Infarction in Mexican Patients

“…The role of the -1575 G/A polymorphism as a susceptibility marker for several diseases is controversial, with positive and negative results reported in the international literature. An association was observed in colorectal cancer 33) and systolic heart failure 34) , whereas no association was reported in periodontitis 35) , diabetic retinopathy 36) , psoriasis 37) , and coronary triple-vessel dis- .05 Sample output of association models for binary response. Four inheritance models are fitted, which correspond to different parameters or groups of genotypes.…”

Combination of retinoids and narrow-band ultraviolet B inhibits matrix metalloproteinase 13 expression in HaCaT keratinocytes and a mouse model of psoriasis

“…Matrix metalloproteinases (MMPs) are structurally related zinc-dependent endopeptidases capable of degradation of extracellular matrix (ECM) 4 , 5 . Dysregulation of MMPs such as MMP2 and MMP9 is frequently detected in patients with psoriasis 6 , 7 , suggesting an involvement of MMPs in psoriasis. MMP13 shows the ability to regulate multiple pathological processes such as arthritis, infection, and tumor progression 5 , 8 .…”