TY - JOUR
T1 - Association between the surfactant protein A (SP-A) gene locus and respiratory-distress syndrome in the Finnish population
AU - Rämet, Mika
AU - Haataja, Ritva
AU - Marttila, Riitta
AU - Floros, Joanna
AU - Hallman, Mikko
N1 - Funding Information:
We are grateful to Ms. Mirkka Parviainen and Ms. Maarit Hännikäinen, for excellent technical assistance, and to Juha Turtinen, M.Sc., Prof. Charles Berry (University of California, San Diego), and Pekka Uimari, Ph.D., for their skillful advice regarding statistics. We are grateful to Drs. Marja-Leena Pokela and Outi Tammela, for the collection of blood specimens; to Professor Mikael Knip, for the contribution of dried blood samples; and to Ms. Eija Rautio, for collection of clinical data. This study was supported by grants from the Foundation for Pediatric Research (to M.R. and M.H.), the Academy of Finland (to M.R. and M.H.), and Biocenter Oulu (to M.H.) and by grant R37 HL34788 from the National Institutes of Health (to J.F.).
PY - 2000
Y1 - 2000
N2 - Respiratory-distress syndrome (RDS) in the newborn is a major cause of neonatal mortality and morbidity. Although prematurity is the most-important risk factor for RDS, the syndrome does not develop in many premature infants. The main cause of RDS is a deficiency of pulmonary surfactant, which consists of phospholipids and specific proteins. The genes underlying susceptibility to RDS are insufficiently known. The candidate-gene approach was used to study the association between the surfactant protein A (SP-A) gene locus and RDS in the genetically homogeneous Finnish population. In the present study, 88 infants with RDS and 88 control infants that were matched for degree of prematurity, prenatal glucocorticoid therapy, and sex were analyzed for SP-A genotypes. We show that certain SP-A1 alleles (6A2 and 6A3) and an SP- A1/SP-A2 haplotype (6A2/1A0) were associated with RDS. The 6A2 allele was overrepresented and the 6A3 allele was underrepresented in infants with RDS. These associations were particularly strong among small premature infants born at gestational age <32 wk. In infants protected from RDS (those that had no RDS, despite extreme prematurity and lack of glucocorticoid therapy), compared with infants that had RDS develop despite having received glucocorticoid therapy, the frequencies of 6A2 (.22 vs. .71), 6A3 (.72 vs. .17), 6A2/1A0 (.17 vs. .68), 6A3/1A1 (.39 vs. .10), and 6A3/1A2 (.28 vs. .06) in the two groups, respectively, were strikingly different. According to the results of conditional logistic-regression analysis, diseases associated with premature birth did not explain the association between the odds of a particular homozygous SPA1 genotype (6A2/6A2 and 6A3/6A3) and RDS. In the population evaluated in the present study, SP-B intron 4 variant frequencies were low and had no detectable association with RDS. We conclude that the SP-A gene locus is an important determinant for predisposition to RDS in premature infants.
AB - Respiratory-distress syndrome (RDS) in the newborn is a major cause of neonatal mortality and morbidity. Although prematurity is the most-important risk factor for RDS, the syndrome does not develop in many premature infants. The main cause of RDS is a deficiency of pulmonary surfactant, which consists of phospholipids and specific proteins. The genes underlying susceptibility to RDS are insufficiently known. The candidate-gene approach was used to study the association between the surfactant protein A (SP-A) gene locus and RDS in the genetically homogeneous Finnish population. In the present study, 88 infants with RDS and 88 control infants that were matched for degree of prematurity, prenatal glucocorticoid therapy, and sex were analyzed for SP-A genotypes. We show that certain SP-A1 alleles (6A2 and 6A3) and an SP- A1/SP-A2 haplotype (6A2/1A0) were associated with RDS. The 6A2 allele was overrepresented and the 6A3 allele was underrepresented in infants with RDS. These associations were particularly strong among small premature infants born at gestational age <32 wk. In infants protected from RDS (those that had no RDS, despite extreme prematurity and lack of glucocorticoid therapy), compared with infants that had RDS develop despite having received glucocorticoid therapy, the frequencies of 6A2 (.22 vs. .71), 6A3 (.72 vs. .17), 6A2/1A0 (.17 vs. .68), 6A3/1A1 (.39 vs. .10), and 6A3/1A2 (.28 vs. .06) in the two groups, respectively, were strikingly different. According to the results of conditional logistic-regression analysis, diseases associated with premature birth did not explain the association between the odds of a particular homozygous SPA1 genotype (6A2/6A2 and 6A3/6A3) and RDS. In the population evaluated in the present study, SP-B intron 4 variant frequencies were low and had no detectable association with RDS. We conclude that the SP-A gene locus is an important determinant for predisposition to RDS in premature infants.
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U2 - 10.1086/302906
DO - 10.1086/302906
M3 - Article
C2 - 10762543
AN - SCOPUS:0033926355
SN - 0002-9297
VL - 66
SP - 1569
EP - 1579
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -