Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory distress syndrome (RDS) and possible race differences

Authors: Floros, J¹; Fan, R²; Matthews, A²; DiAngelo, S¹; Luo, J¹; Nielsen, H³; Dunn, M⁴; Gewolb, I H⁵; Koppe, J⁶; van Sonderen, L⁶; Farri-Kostopoulos, L⁷; Tzaki, M⁸; Rämet, M; Merrill, J⁹

Source: Clinical Genetics, Volume 60, Number 3, September 2001 , pp. 178-187(10)

Publisher: Blackwell Publishing

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Abstract:

A key cause of respiratory distress syndrome (RDS) in the prematurely born infant is deficiency of pulmonary surfactant, a lipoprotein complex. Both low levels of surfactant protein A (SP-A) and SP-A alleles have been associated with RDS. Using the candidate gene approach, we performed family-based linkage studies to discern linkage of SP-A to RDS and identify SP-A susceptibility or protective alleles. Moreover, we performed case-control studies of whites and blacks to detect association between RDS and SP-A alleles. Transmission disequilibrium test (TDT) analysis revealed that the frequency of transmission (from parent to the offspring with RDS) of alleles 6A² and 1A⁰ and of 1A⁰/6A² haplotype in RDS was increased, whereas transmission of alleles 1A⁵ and 6A⁴ and of haplotype 1A⁵/6A⁴ was decreased. Extended TDT analysis further strengthened the observations made. The case-control studies showed that in whites or blacks with RDS the frequencies of specific genotypes, 1A⁰ and 6A² or 1A⁰, were increased, respectively, but the frequency of specific 6A³ genotypes was increased in certain white subgroups and decreased in blacks. Regression analysis revealed gestational age (GA) and 6A³ genotypes are significant factors in blacks with RDS. In whites with RDS, GA and antenatal steroids are important factors. The data together indicate linkage between SP-A and RDS; certain SP-A alleles/haplotypes are susceptibility (1A⁰, 6A², 1A⁰/6A²) or protective (1A⁵, 6A⁴, 1A⁵/6A⁴) factors for RDS. Some differences between blacks and whites with regard to SP-A alleles may exist.

Keywords: ETDT, extended TDT; race differences; RDS, respiratory distress syndrome; SP-A variants; TDT, transmission disequilibrium test

Document Type: Research article

DOI: 10.1034/j.1399-0004.2001.600303.x

Affiliations: 1: Departments of Cellular and Molecular Physiology, 2: Health Evaluation Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, USA, 3: Department of Pediatrics, New England Medical Center, Boston, MA, 4: Department of Pediatrics, University of Toronto, Toronto, Canada, 5: Department of Pediatrics, University of Maryland, Baltimore, MD, USA, 6: Department of Neonatology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 7: Department of Pediatrics, University of Patras, Patras, Greece, 8: Department of Neonatology, Elena Hospital, Athens, Greece, 9: Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA

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