Analysis of two polymorphisms in the promoter region of matrix metalloproteinase 1 and 3 genes in women with endometriosis.
BACKGROUND
Matrix metalloproteinases are a family of proteolytic enzymes that can degrade extracellular matrix components and have been implicated in connective tissue remodeling associated with cancer invasion and metastasis. These proteins are also involved in the invasive events underlying endometriotic lesion formation and aggressive behavior. Given the established genetic background of endometriosis, the aim of this study was to examine the potential impact of two polymorphisms in the gene promoter region of two of these enzymes, matrix metalloproteinases 1 and 3, on predisposition and severity of the disease.


METHODS
Genomic DNA was obtained from 56 Italian Caucasian women with a surgical diagnosis of endometriosis and a control group of 71 age-matched Caucasian healthy female blood donors. In control women, endometriosis was ruled out by evaluation of the medical history, gynecologic examinations, and ultrasound scanning. Two polymorphisms have been specifically investigated: 1. a single insertion polymorphism (2G) in the matrix metalloproteinase-1 promoter region known to elevate transcriptional level of matrix metalloproteinase-1; and 2. a single insertion/deletion polymorphism (5A/6A) located in the promoter of the matrix metalloproteinase-3 gene with functional significance in the regulation of its expression. Genotypes were determined by PCR amplification and sequence analysis.


RESULTS
Allele and genotype frequencies of both polymorphisms did not significantly differ between endometriosis and control groups. Moreover, no significant difference for both polymorphisms was observed in relation to the clinical stage and recurrence status of the disease.


CONCLUSIONS
This is the first study that has evaluated the possibility that gene variants of matrix metalloproteinases might be involved in the susceptibility to endometriosis. However, these results suggest that matrix metalloproteinases 1 and 3 promoter polymorphism do not constitute an important factor for the genetic predisposition to endometriosis and its invasive behavior in the Italian population.
Ferrari
Maria Maddalena
MM
Department of Obstetrics, Gynecology and Neonatology, Clinica "L. Mangiagalli", San Paolo Hospital, University of Milan, Milan, Italy.
Biondi
Maria Luisa
ML
Rossi
Gabriela
G
Grijuela
Barbara
B
Gaita
Sara
S
Perugino
Giuseppe
G
Viganò
Paola
P
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004715:Endometriosis / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1