Published genetic variants in retinopathy of prematurity: random forest analysis suggests a negligible contribution to risk and severity.
OBJECTIVE
Our recent investigations suggested association between severe retinopathy of prematurity (ROP) and some genetic polymorphisms contributing to angiogenesis. While these findings may help to identify specific elements in ROP pathogenesis, the predictive value of these genetic variants at birth is unknown. We applied a high-dimensional nonparametric method called random forest technique (RFT) to evaluate the predictive value of genetic polymorphisms in ROP at birth.


METHODS
We used published genetic (i.e., VEGF T(-460)C, G(+ 405)C, and C(-2578)A; IGF-I receptor G(+ 3174)A, angiopoietin II G(-35)C; estrogen receptor PvuII Pp; and endothelial NO-synthase 27-bp b/a and T(-786)C) and birth data of 134 preterm infants without and 103 preterm infants with ROP requiring laser or cryotherapy. We used RFT to determine the relative importance scores (IS) of each clinical parameter at birth and genetic polymorphisms in the prediction of ROP. The accuracy of ROP prediction at birth was calculated when birth data, genotype data, and birth data PLUS genotype data were taken into account.


RESULTS
The most important predictors of ROP were prematurity, low birth weight, intrauterine retardation, and Apgar scores with IS values between 7.46 and 13.20. IS values of genotype data were much lower in the range between 0.86 and 4.19. When birth data solely, genotype data solely, and birth data plus genotype data together were used for prediction, the accuracy of prediction was 0.653, 0.636, and 0.674, respectively.


CONCLUSIONS
The tested genetic polymorphisms (including those published as significant risk factors of ROP) are not good predictors of ROP at birth.
Dunai
György
G
Csolnoky Ferenc Hospital, Veszprem, Hungary.
Vásárhelyi
Barna
B
Szabó
Miklós
M
Hajdú
Júlia
J
Mészáros
Gergõ
G
Tulassay
Tivadar
T
Treszl
András
A
D042702:Angiopoietin-2 / Q000235:genetics; D005260:Female; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011110:Polymorphism, Genetic; D017526:Receptor, IGF Type 1 / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D012178:Retinopathy of Prematurity / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D042702:Angiopoietin-2; D011960:Receptors, Estrogen; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D017526:Receptor, IGF Type 1