Further Observations on Associations Between the ADA Gene and Past Malaria Morbidity in Sardinia.

Objectives: Adenosine Deaminase (ADA) contributes to the regulation of adenosine concentration and in turn to T cell activation. Genetic variability of ADA activity may have, therefore, an important role in resistance to malaria. Indeed, previous studies in Sardinia have shown a lower frequency of ADA1*2 allele (associated with low ADA activity) in areas, where malaria was heavily endemic compared to areas where malaria was not endemic. We have now studied the ADA2 locus, another polymorphic site with two alleles ADA2 *1 and ADA2 *2 within the ADA gene. Methods: In the area of Oristano (where malaria was endemic in the past) 51 consecutive newborns and in the area of Nuoro (where malaria was not as endemic) 48 consecutive newborns were examined. ADA1 and ADA2 genotypes were determined by DNA analysis. Results: The low frequency of the ADA1*2 allele in the area where malaria was endemic is confirmed. The frequency of the ADA2*2 allele is higher in Oristano than in Nuoro resulting in a higher frequency of the ADA1*1/ADA2*2 haplotype in Oristano as compared to Nuoro. This suggests a selective advantage of this haplotype in a malarial environment. Conclusions: The ADA gene shows other polymorphic sites further studies on their role in human adaptation to malaria could be rewarding.