Genetic polymorphisms of matrix metalloproteinase 12 and 13 genes are implicated in endometriosis progression

• Published in: Human reproduction (Oxford) Vol. 23; no. 5; pp. 1207 - 1213
• Main Authors: Borghese, Bruno, Chiche, Jean-Daniel, Vernerey, Déwi, Chenot, Claire, Mir, Olivier, Bijaoui, Gérard, Bonaiti-Pellié, Catherine, Chapron, Charles
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Biological and medical sciences; Case-Control Studies; combination test; Disease Progression; Endometriosis; Endometriosis - genetics; Female; Gene Frequency; genetics; Gynecology. Andrology. Obstetrics; Humans; Linkage Disequilibrium; matrix metalloproteinase; Matrix Metalloproteinase 12 - genetics; Matrix Metalloproteinase 13 - genetics; Medical sciences; polymorphism; Polymorphism, Genetic; Polymorphism, Single Nucleotide; endometriosis; matrix metalloproteinase; polymorphism; genetics; combination test; Enzyme; Endometriosis; Exploration; Metalloendopeptidases; Female genital diseases; Peptidases; Vertebrata; Mammalia; Gene; Test; Uterine diseases; Hydrolases; Genetics; Polymorphism
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/den007

BACKGROUND Matrix metalloproteinases (MMPs) may contribute to endometriosis. We tested whether eight functional polymorphisms of these genes could modify the risk of endometriosis. METHODS In this case–control study, 227 endometriosis and 241 controls were genotyped for MMP1 –1607 1G/2G, MMP2 –1575 G/A (MMP2.1), –1306 C/T (MMP2.2), MMP3 –1612 5A/6A, MMP7 –153 C/T (MMP7.1), –181 A/G (MMP7.2), MMP12 –82 A/G and MMP13–77 A/G. Association between MMP genotypes and superficial (SUP), deep infiltrating (DIE) and endometriomas (OMA) was tested for each polymorphism separately, using unconditional logistic regression and then for combined genotypes, using the combination test. RESULTS When considering all cases, MMP2 polymorphisms were found to be significant, mainly due to DIE (P = 0.023). A small difference between SUP and controls was found for MMP7.2 (P = 0.032) and MMP12 (P = 0.035), in the absence of correction for multiple testing. Using the combination test, the best association when comparing SUP with controls was obtained for MMP12–MMP13 (P = 0.004) for the combined genotype A/G–A/A (odds ratio = 27.60, 95% confidence interval: 2.80–272.40). CONCLUSIONS These data show a potential role for MMP12 –82 A/G and MMP13 –77 A/G combined polymorphisms in superficial endometriosis. As no association was found with deep infiltrating endometriosis, this combination of polymorphisms might protect from a more in-depth penetration of tissues.