Genetic variation in tissue inhibitors of metalloproteinases as a risk factor for idiopathic recurrent spontaneous abortion

There were no statistically significant differences in the distribution of genotype and allele frequencies of tissue inhibitors of metalloproteinases 1, 2, 3, and 4 gene polymorphisms between idiopathic recurrent spontaneous abortion couples and control subjects.

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Nina Pereza, M.D., Marija Volk, M.D., Nikolina Zrakić, Miljenko Kapović, M.D., Ph.D., Borut Peterlin, Ph.D., M.D., Saša Ostojić, Ph.D., M.D.

Volume 99, Issue 7, Pages 1923-1929, June 2013



To investigate the potential association of tissue inhibitor of metalloproteinases (TIMP) 1, 2, 3, and 4 gene polymorphisms with idiopathic recurrent spontaneous abortion (IRSA).


Case-control and association study.


Departments of gynecology and obstetrics and university-based research laboratory.


A total of 149 couples with a history of three or more idiopathic spontaneous pregnancy losses and 149 fertile men and 149 fertile women with at least two live births and no history of pregnancy pathologies.


Polymerase chain reaction and restriction-fragment-length polymorphism methods.

Main Outcome Measure(s):

Detection of TIMP-1 −372 C/T, TIMP-2 −303 C/T, TIMP-3 −915 A/G, TIMP-3 −1296 C/T, and TIMP-4 −3′-UTR C/T genotypes and allele frequencies.


There were no statistically significant differences in the distribution of any genotype and allele frequencies or any genetic model between IRSA patients and controls. Additionally, no significant associations occurred between combinations of TIMP polymorphisms and the risk of IRSA.


We found no evidence for the association of TIMP-1, -2, -3, and -4 with IRSA in a Slovenian population.

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