University of Oulu

The role of surfactant protein A and B genes in heritable susceptibility to neonatal respiratory distress syndrome

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Author: Haataja, Ritva1,2
Organizations: 1University of Oulu, Faculty of Medicine, Department of Paediatrics
2University of Oulu, Biocenter Oulu
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
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Language: English
Published: 2001
Publish Date: 2001-10-18
Thesis type: Doctoral Dissertation
Defence Note: Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium L12 of the Department of Paediatrics, University Hospital of Oulu, on December 5th, 2001, at 12 noon.
Reviewer: Professor Leena Palotie
Professor Marja-Liisa Savontaus


Respiratory distress syndrome (RDS) is a disease characterized by neonatal respiratory failure. It is principally caused by a deficiency of pulmonary surfactant, which is a lipoprotein mixture essential for reducing surface tension at the air-liquid interface of the alveolus. Prematurity is the major risk factor predisposing to RDS. Several pieces of evidence suggest the role of genetic factors in the susceptibility to this multifactorial disease.

The present study was performed to determine whether polymorphisms of the surfactant protein SP-A1, SP-A2 and SP-B genes associate with RDS and to evaluate the relative contributions of genetic and environmental factors to the disease etiology. Allelic associations between the candidate genes and RDS were investigated using a matched and unmatched case-control and family-based study design. Disease concordance in monozygotic vs. dizygotic twin pairs was determined to measure the impact of heredity in RDS.

SP-A and SP-B genes were shown to play a significant role in susceptibility to RDS. In very premature singleton infants born before 32 weeks of gestation, SP-A1 and SP-A2 allelic variations were associated with RDS, whereas the SP-B gene showed no direct association. Instead, the association between the high-risk (6A2, 1A0) or low-risk (6A3, 1A1/1A2) SP-A alleles and RDS was dependent on SP-B Ile131Thr variation, being restricted to a subset of infants carrying the homozygous genotype Thr/Thr. No allelic associations were evident in premature infants born after 32 weeks of gestation.

RDS concordance was not significantly higher in monozygotic than in dizygotic twin pairs, implying a non-genetic disease etiology. However, the present study suggests that the concordance difference underestimates the extent of heredity. Twin pregnancies include intrauterine environmental factors that complicate the interpretation of the hereditary impact. SP-B Ile131Thr variation was associated with RDS in the first-born, but not in the second-born twins.

The present results indicate that susceptibility to RDS is highly heterogeneous, involving complex environmental and genetic interactions. The degree of prematurity, singleton vs. multiple pregnancy, and birth order in a multiple birth are environmental confounders that determine disease subgroups. Genetic variations in the SP-A and SP-B genes account for part of the genetic component of RDS.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 951-42-6525-4
ISBN Print: 951-42-6524-6
Issue: 651
Copyright information: © University of Oulu, 2001. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.