Association of interferon gamma T+874A and interleukin 12 p40 promoter CTCTAA/GC polymorphism with the need for respiratory support and perinatal complications in low birthweight neonates.
BACKGROUND
Data support the role of interferon (IFN)gamma and interleukin (IL)12 in perinatal complications. IFNgamma T(+874)A and IL12 p40 promoter CTCTAA/GC polymorphisms may have an effect on cytokine production.


METHODS
DNA was extracted from dried blood samples of 153 low birthweight (LBW) infants and 172 healthy term infants. IFNgamma and IL12 genetic polymorphisms were determined to investigate the association between polymorphisms and ventilation characteristics, bronchopulmonary dysplasia (BPD) and other perinatal disorders.


RESULTS
The IFNgamma(+874)A allele was over-represented in LBW infants. Carriers of the IFNgamma(+874)T allele required mechanical ventilation and oxygen supplementation for time periods 41% and 35%, respectively, shorter than those required by those not carrying the IFNgamma(+874)T allele. Stepwise logistic regression analysis showed that carriers of the IFNgamma(+874)T allele were protected against BPD (odds ratio (OR) 0.35 (95% confidence interval (CI) (0.12 to 0.99))) and patent ductus arteriosus (OR 0.43 (95% CI 0.19 to 0.97)), whereas carriers of the IFNgamma(+874)A allele were at higher risk of severe hypotension (OR 3.40 (95% CI 1.01 to 11.52)) and respiratory distress syndrome (OR 4.03 (95% CI 1.30 to 12.50)). Carriers of the IL12 GC allele were protected against pneumonia (OR 0.32 (95% CI 0.14 to 0.75)). Carriers of the IL12 CTCTAA allele were at higher risk of developing necrotising enterocolitis (NEC; OR 2.37 (95% CI 1.01 to 5.53)).


CONCLUSIONS
Carrier state of the IFNgamma(+874)A allele presents an increased risk for premature birth and lung damage, as well as other perinatal complications. The risks of pneumonia and NEC are higher in heterozygotic carriers of the IL12 CTCTAA/GC polymorphism. Further studies are needed to determine whether these associations are the result of altered cytokine-producing capacity in infants carrying the tested alleles.
Bokodi
G
G
First Department of Pediatrics, Semmelweis University, Budapest, Hungary. bokodi@gyer1.sote.hu
Derzbach
L
L
Bányász
I
I
Tulassay
T
T
Vásárhelyi
B
B
D000483:Alleles; D001997:Bronchopulmonary Dysplasia / Q000235:genetics; D004374:Ductus Arteriosus, Patent / Q000235:genetics; D020345:Enterocolitis, Necrotizing / Q000235:genetics; D005260:Female; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007022:Hypotension / Q000235:genetics; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000235:genetics*; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D008297:Male; D011014:Pneumonia / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D012121:Respiration, Artificial / Q000379:methods; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors
D053762:Interleukin-12 Subunit p40; D007371:Interferon-gamma