The ADA*2 Allele of the Adenosine Deaminase Gene and Recurrent Spontaneous Abortions in Northwest of Iran

Recurrent spontaneous abortion (RSA) is defined by two or more consecutive miscarriages before 20 weeks of gestation. Adenosine deaminase (ADA) is an enzyme of purine salvage pathway and has two important isoenzymes ADA1 and ADA2. The adenosine deaminase G22A polymorphism (ADA*2) increases the level of adenosine. Adenosine may play a protective role against recurrent spontaneous abortions, since it regulates blood flow into the uterus and placenta. In consideration of the effect of decreased enzymatic activity of adenosine deaminase G22A polymorphism on adenosine levels we evaluated the protective effect of ADA*2 allele against recurrent spontaneous abortions in north-west of Iran. A total of 100 women were recruited to form two groups. First one, with a history of recurrent spontaneous abortions (N=50), and the second one, without a history of abortions (N=50). Genomic DNA was extracted from peripheral blood with a commercial kit and PCR-RFLP analysis was used to identify the G22A genetic polymorphism. Fisher's exact test and odds ratio values were used to compare the proportions of adenosine deaminase genotypes and alleles between women with and without a history of recurrent spontaneous abortion (p<0.05). The frequency of homozygotes (AA) was 2% in control group, whereas no homozygote (AA) was found in the case group. The frequency of heterozygotes (AG) was 20% in control group and 8% in the case group (p<0.05). The frequency of homozygotes (GG) was 78% in control group and 92% in the case group (p<0. 05). A significant increase in the frequency of AG genotype in controls (p=0.014, OR=0.348) relative to women with the history of RSA demonstrates the protective effect of AG genotype in controls. The data suggest that women carrying the G22A polymorphism (ADA*2 allele) and AG genotype which is associated with the lower enzymatic activity are better protected against recurrent spontaneous abortions.