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 < or =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.

Protection from Abortion by Heme Oxygenase-1 Up-Regulation Is Associated with Increased Levels of Bag-1 and Neuropilin-1 at the Fetal-Maternal Interface

“…It remains to be elucidated whether the low HOs levels are a consequence of the fetal tissue damage or the cause of abortion (i.e., due to a different genetic background in the F 1 tissue). Accordingly, Denschlag et al (36) observed that a microsatellite polymorphism of the HO-1 gene (leading to low levels of HO-1 expression) is associated with ). Statistical analysis was done by using the nonparametric Kruskall-Wallis test followed by Mann-Whitney U test.…”

Reduced Expression of Heme Oxygenase-1 in Patients with Coronary Atherosclerosis

“…HO-1 mRNA expression was quantified by real-time PCR (Light Cycler Instrument; Roche Diagnostics, Basel, Switzerland) utilizing glyceraldehyde-3-phosphate dehydrogenase (GAPD) as an internal standard. Primers were synthesized according to the published sequences (35). Standard curves were prepared for the target and reference genes by amplification of diluted plasmid DNA containing the target sequences (pGem+ vector; Promega Corp., Madison, USA).…”

American Pediatric Society Presidential Address 2006: Science on the Edge With Life in the Balance

“…Length of these repeats is associated with variability in basal HO-1 gene expression levels and disease states (12,14). One example of a human HO-1 deficiency has been reported from Japan (15).…”