Abstract
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.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-6525-4 |
| Date | 18 October 2001 |
| Creators | Haataja, R. (Ritva) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2001 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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