Matrix metalloproteinases’s association of polymorphisms of MMP3 and MMP9 with development of genital endometriosis

In: Russian Journal of Genetics · 2014 · vol. 50(2) , pp. 205–210 · doi:10.1134/s1022795414010128 · W2092691632
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This study found significant differences in MMP3 and MMP9 alleles between women with external genital endometriosis and controls, suggesting a role for matrix metalloproteinases in disease pathogenesis.

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This study compared allelic polymorphisms in multiple matrix metalloproteinase genes (including MMP3 rs3025058 and MMP9 rs17576, rs2250889) between women with external genital endometriosis (EGE) and healthy controls confirmed disease-free by laparoscopic inspection. The authors found significant differences in the incidence of particular MMP3 and MMP9 alleles and used multifactor dimensionality reduction to identify statistically significant multi-SNP allele combinations involving MMP3 × MMP7 × MMP9 that were associated with increased EGE risk (14 risk combinations) or decreased risk (10 protective combinations). Two MDR models for MMP allele combinations showed 100% penetrance with 83% and 78% accuracy. The paper’s main caveat is that, based on the provided abstract, it focuses on genetic association without reporting functional validation of how these variants alter MMP activity or endometriosis biology. This paper is centrally about endometriosis — it specifically tests associations between MMP3/MMP9 polymorphisms and development of external genital endometriosis using MDR gene–gene interaction models.

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Abstract

We present a comparative analysis of the allelic polymorphisms of the matrix metalloproteinase (MMP) gene family, including MMP3 (rs3025058), MMP7 (rs11568818), MMP9 (rs17576, rs2250889), MMP12 (rs2276109), and MMP13 (rs2252070), in patients with external genital endometriosis (EGE) and in a control group of healthy women proven to be free of disease by laparoscopic inspection. We found significant differences in the incidence of particular MMP3 and MMP9 alleles, which substantiate the role of matrix metalloproteinases in EGE pathogenesis. We used the Multifactor Dimensionality Reduction (MDR) analysis to show that 14 allelic combinations of the MMP containing MMP3 (rs3025058) × MMP7 (rs11568818) × MMP9 (rs17576) alleles showed a statistically significant association with an increased risk of EGE, while 10 other combinations correlated with a reduced risk of the disease. MDR analysis produced two statistically significant models for MMP allelic combinations involved in EGE progression, both with 100% penetrance and 83 and 78% accuracy.
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Abstract

We present a comparative analysis of the allelic polymorphisms of the matrix metalloproteinase (MMP) gene family, including MMP3 (rs3025058), MMP7 (rs11568818), MMP9 (rs17576, rs2250889), MMP12 (rs2276109), and MMP13 (rs2252070), in patients with external genital endometriosis (EGE) and in a control group of healthy women proven to be free of disease by laparoscopic inspection. We found significant differences in the incidence of particular MMP3 and MMP9 alleles, which substantiate the role of matrix metalloproteinases in EGE pathogenesis. We used the Multifactor Dimensionality Reduction (MDR) analysis to show that 14 allelic combinations of the MMP containing MMP3 (rs3025058) × MMP7 (rs11568818) × MMP9 (rs17576) alleles showed a statistically significant association with an increased risk of EGE, while 10 other combinations correlated with a reduced risk of the disease. MDR analysis produced two statistically significant models for MMP allelic combinations involved in EGE progression, both with 100% penetrance and 83 and 78% accuracy. Similar content being viewed by others

References

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