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-A I, 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 t he 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 c odon 131 (Thr131Ile) of the SP-B gene. The latter determines the presence o r absence of a potential N-linked glycosylation site. Multivariate analysis revealed significant differences only for the C/T (1580) polymorphism. Whe n the ARDS population was divided into subgroups, idiopathic (i.e., pneumon ia, etc.) or exogenic (i.e., trauma, etc.), significant differences were ob served 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 th e 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.