Molecular Human Reproduction, Vol. 10, No. 3, pp. 211-214, 2004
© European Society of Human Reproduction and Embryology 2004
The size of a microsatellite polymorphism of the haem oxygenase 1 gene is associated with idiopathic recurrent miscarriage
1Department of Obstetrics and Gynecology, University of Freiburg School of Medicine, Hugstetter Strasse 55, D-79106 Freiburg, Germany, 2Department of Laboratory Medicine and 3Department of Obstetrics and Gynecology, University of Vienna School of Medicine, Vienna, Austria *These two authors contributed equally to this paper
4 To whom correspondence should be addressed. e-mail: tempfer{at}frk.ukl.uni-freiburg.de
Endothelial damage, impaired microvascularization and immune maladaptation have been described as aetiological factors in recurrent miscarriages. We investigated the relationship between idiopathic recurrent miscarriage (IRM) and a (GT)n repeat microsatellite polymorphism of the gene encoding haem oxygenase 1 (HO-1), known to modulate immune functions such as T-helper (TH) cell function and to be associated with cardiovascular disease. We investigated 162 women with IRM and 129 healthy, post-menopausal controls. The length of the HO-1 (GT)n microsatellite was assessed by PCR and direct sequencing in all women. Results were correlated with clinical data. The distribution of genotypes was in HardyWeinberg equilibrium. The HO-1 (GT)n microsatellite repeat numbers ranged from 13 to 37, with (GT)23 and (GT)30 being the most common alleles in both groups. We compared alleles consisting of
27 GT repeats, termed class S (short) alleles and alleles consisting of >28 GT repeats, termed class L (long) alleles. Seventy per cent of women with IRM had an S allele either in heterozygous (L/S) or homozygous (S/S) form, compared to 56% of controls (P = 0.02; OR 0.54; 95% CI 0.320.90). With respect to S allele frequencies, we found no significant difference among women with IRM and controls [P = 0.3; odds ratio (OR) 1.23, 95% confidence interval (CI) 0.861.76]. Comparing women with primary and secondary IRM, no difference with respect to the length of the HO-1 (GT)n microsatellite was ascertained. In summary, this is the first report on a HO-1 (GT)n microsatellite polymorphism among women with IRM, demonstrating that the investigated polymorphism is associated with IRM in a relatively large Caucasian population.
Key words: Key words: idiopathic recurrent miscarriage/haem oxygenase 1/microsatellite/polymorphism risk factor
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