ADA genetic polymorphism and the effect of smoking on neonatal bilirubinemia and developmental parameters

Division of Biopathology of Human Populations and Environmental Pathology, University of Rome Tor Vergata, School of Medicine, Rome, Italy.
Early Human Development (Impact Factor: 1.79). 07/2008; 84(11):739-43. DOI: 10.1016/j.earlhumdev.2008.05.001
Source: PubMed


Genetic variability of metabolic enzymes may influence the effect of cigarette smoking on intrauterine development and on early neonatal events.
To investigate the role of adenosine deaminase genetic polymorphism on the effect of smoking on neonatal bilirubinemia and developmental parameters.
Analysis of association between adenosine deaminase phenotypes and neonatal developmental parameters. Prospective study of serum bilirubin level in relation to adenosine deaminase phenotype.
We have studied 360 consecutive newborn infants from the Caucasian population of Rome. Serum bilirubin concentration was determined at birth and every 24 h for the first five days.
Overall maternal smoking is associated with a slight decrease in the incidence of phototherapy (13.4% in non smoking vs 11.7% in smoking mothers) and with a reduction of birth weight (3374 g in non smoking mothers vs 3133 g in smoking mothers). There is a significant interaction between smoke and adenosine deaminase. While in non smoking mothers the incidence of phototherapy in carriers of ADA 2 allele is higher than in ADA 1 phenotype, in infants from smoking mothers the pattern is reversed and the incidence of phototherapy in carriers of ADA 2 allele is lower than in infants with ADA 1 phenotype. Other neonatal bilirubin parameters follow a similar pattern of interaction between smoking and ADA. The negative effect of smoke on birth weight is much more evident in infant with ADA 1 phenotype than in those carrying the ADA 2 allele.
The data suggest that ADA phenotype modifies the effect of smoking on developmental and bilirubin parameters.

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    • "Previous studies by our group have shown an association of Adenosine Deaminase locus 1 (ADA1) polymorphisms with allergic manifestations in children and adults (7, 8) and with bilirubin levels in the newborn (9, 10). This suggests that the effects of ADA on susceptibility to allergy could be correlated with the effects of ADA on bilirubin levels. "
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    ABSTRACT: Several studies suggest a protective role of bilirubin against oxidative damage during the neonatal period. ADA1*2 allele has been found associated with higher bilirubin levels in newborns and with a protective action against bronchial asthma. Thus the relation between ADA1 and asthma could be mediated by events occurring during the early extrauterine life. Moreover the increased prevalence of allergic diseases in western populations parallels the widespread practice of phototherapy during the neonatal period. These observations prompted us to reevaluate our previous data and show new observations. Data from 2729 previously studied subjects, from 53 subjects studied at birth and after 30 years and from a survey of phototherapy frequency in four Italian Hospital including 7392 newborns are reported. ADA1*2 allele carriers are less represented among asthmatic subjects than in controls (p=0.0004). ADA1*2 allele carriers among newborns undergoing phototherapy for hyperbilirubinemia is higher when compared to newborns not undergoing this treatment (p=0.006). In infants treated by phototherapy, the maximum bilirubin level attained during the first few days of life positively correlated with the ADA1*2 allele dose (p=0.001). Among subjects studied at birth, allergic rhinitis and/or conjunctivitis are more frequent among those treated with phototherapy than among those not treated (p=0.046). These observations support our hypothesis that ADA1*2 allele through an increase of bilirubin level in the neonatal period protects infants from oxidative stress and favours Th2→Th1 switching thus preventing allergic manifestations in later periods of life.
    03/2010; 6(1):8-12.
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    • "We have observed that the proportion of carriers of ADA*2 allele in newborns who have undergone phototherapy for high bilirubin level during the first few days of life is higher as compared to those who have not undergone such treatment [21, 22]. On the other hand the proportion of carriers of ADA*2 allele is lower in CAD than in healthy subjects [1]. "
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    ABSTRACT: An inverse relationship between birth weight and coronary artery diseases is well documented but it remains unclear which exposure in early life might underlie such association. Recently it has been reported an association between adenosine deaminase genetic polymorphism and coronary artery diseases. Gender differences in the degree of this association have been also observed. These observations prompted us to study the possible joint effects of BW, ADA, and gender on the susceptibility to coronary artery diseases. 222 subjects admitted to hospital for nonfatal coronary artery diseases, and 762 healthy consecutive newborns were studied. ADA genotypes were determined by DNA analysis. A highly significant complex relationship has emerged among ADA, birth weight, and gender concerning their role on susceptibility to coronary artery diseases in adult life. Odds ratio analysis suggests that low birth weight is more important in females than in males. ADA( *)2 allele appears protective in males, while in females such effect is obscured by birth weight.
    Cardiology Research and Practice 01/2009; 2009:860328. DOI:10.4061/2009/860328

  • Cardiology 06/2009; 114(2):100-1; author reply 102. DOI:10.1159/000217743 · 2.18 Impact Factor
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