MMP-2和TIMP-2基因多态性与子宫内膜异位症和子宫腺肌病发病风险的关联研究

Study on the association of SNPs of MMP-2 and TIMP-2 genes with the risk of endometriosis and adenomyosis

目的探讨基质金属蛋白酶-2（matrix metalloproteinase-2，MMP-2）和金属蛋白酶组织抑制剂-2（tissue inhibitor of metalloproteinase-2，TIMP-2）基因启动子区单核苷酸多态性与子宫内膜异位症和子宫腺肌病发病风险的关系。方法采用PCR-限制性片段长度多态方法检测298例子宫内膜异位症患者（内异症组）、180例子宫腺肌病患者（腺肌病组）和324名对照妇女（对照组）MMP-2和TIMP-2基因型频率的分布。结果MMP-2—1306C／T多态的基因型和等位基因频率分布在子宫内膜异位症组与对照组间差异无统计学意义（P〉0．05）；但在腺肌病组和对照组间MMP-2—1306C／T多态的基因型和等位基因频率分布均有明显的差异（P〈0．05）；与CT＋TT基因型相比，CC基因型明显增加腺肌病的发病风险，OR值为1．83（95％CI：1．13～2．96）。MMP-2—735C／T多态的基因型和等位基因频率分布在3组间均未发现明显差异（P〉0．05）；统计学分析显示MMP-2基因的2个多态性位点间存在着连锁不平衡（D＇=0．74），但4种单倍型频率在3组之间分布差异无统计学意义（P〉0．05）。TIMP-2—418G／C多态的等位基因频率分布在3组间差异无统计学意义（P〉0．05），但CC基因型频率在子宫内膜异位症组患者中为0．7％，与对照组（3．7％）比较，差异有统计学意义（P〈0．05）。结论MMP-2—1306C／T多态C等位基因的存在可明显增加腺肌病的发病风险，但与子宫内膜异位症的发病风险无关；MMP-2—735C／T和TIMP-2—418G／C多态与子宫内膜异位症和腺肌病的发病风险无明显关联。

Objective To 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. Methods Genotypes 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. Results No 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 = 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）. Conclusion The C allele ofMMP-2 - 1306C/T polymorphism did not modify the risk of developing endometriosis but significantly increase the risk of developing adenomynsis. The MMP-2 - 735C/T and T/MP-2 - 418G/C polymorphisms were not associated with the risk of developing endometriosis or adenomyosis.