The size of a microsatellite polymorphism of the haem oxygenase 1 gene is associated with idiopathic recurrent miscarriage

Abstract

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 Hardy-Weinberg 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 0.32-0.90). 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) 0.86-1.76]. 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. © European Society of Human Reproduction and Embryology 2004; all rights reserved.