OBJECTIVETo investigate the association of single nucleotide polymorphisms (SNPs) in matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) with the risk of endometriosis and adenomyosis.

METHODSGenotypes of MMP-2 and TIMP-2 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method among 298 endometriosis patients, 180 adenomyosis patients and 324 matched control women.

RESULTSNo significant difference was found in allele frequencies and genotype distributions of MMP-2 -1306C/T polymorphism between endometriosis patients and control women (P> 0.05). However, there were significant differences in genotype and allele distributions of MMP-2 -1306C/T polymorphism between adenomyosis patients and control women (P< 0.05). Compared with CT+TT genotypes, CC genotype significantly increases the risk of adenomyosis, with an odds ratio of 1.83 (95% CI was 1.13-2.96). No significant difference was shown in allele frequencies and genotype distributions of the MMP-2 -735C/T polymorphism among the three groups (P>0.05). MMP-2 -1306C/T and -735C/T polymorphisms displayed linkage disequilibrium (D'=0.74). There was no significant difference in haplotype distributions of the two MMP-2 SNPs among the three groups ( P> 0.05). No significant difference was found in allele frequencies of TIMP-2 -418G/C polymorphism among the three groups (P> 0.05). However, the frequency of TIMP-2 CC genotype in endometriosis patients (0.7%) was significantly lower than that in the control women (3.7%) (P< 0.05).

CONCLUSIONThe C allele of MMP-2 -1306C/T polymorphism did not modify the risk of developing endometriosis but significantly increase the risk of developing adenomyosis. The MMP-2 -735C/T and TIMP-2 -418G/C polymorphisms were not associated with the risk of developing endometriosis or adenomyosis.

Adult ; Endometriosis ; genetics ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Linkage Disequilibrium ; genetics ; Matrix Metalloproteinase 2 ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Tissue Inhibitor of Metalloproteinase-2 ; genetics

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β ₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.