Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS.
An allele association study of 19 polymorphisms in surfactant proteins SP-A1, SP-A2, SP-B, and SP-D genes in acute respiratory distress syndrome (ARDS) was carried out. Trend-test analysis revealed differences (p < 0.05) in the frequency of alleles for some of the microsatellite markers flanking SP-B, and for one polymorphism (C/T) at nucleotide 1580 [C/T (1580)], within codon 131 (Thr131Ile) of the SP-B gene. The latter determines the presence or absence of a potential N-linked glycosylation site. Multivariate analysis revealed significant differences only for the C/T (1580) polymorphism. When the ARDS population was divided into subgroups, idiopathic (i.e., pneumonia, etc.) or exogenic (i.e., trauma, etc.), significant differences were observed for the C/T (1580), for the idiopathic ARDS group, and the frequency of the C/C genotype was increased in this group. Based on the odds ratio, the C allele may be viewed as a susceptibility factor for ARDS. Although the expression of both C and T alleles occurs in heterozygous individuals, it is currently not known whether these alleles correspond to similar levels of SP-B protein. These data suggest that SP-B or a linked gene contributes to susceptibility to ARDS.
Lin
Z
Z
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey 17033, USA.
Pearson
C
C
Chinchilli
V
V
Pietschmann
S M
SM
Luo
J
J
Pison
U
U
Floros
J
J
D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers; D005091:Exons / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D005858:Germany; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D008168:Lung / Q000378:metabolism / Q000473:pathology; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics*
D017931:DNA Primers; D006023:Glycoproteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human