Racial Differences in Allelic Distribution at the Human Pulmonary Surfactant Protein B Gene Locus (SP-B)

Abstract

Variable numbers of composite repetitive motifs are found in different individuals within intron 4 of the surfactant protein B (SP-B) gene (Biochem J. 1995;305:583). This study tests the hypothesis that the distribution of SP-B alleles differs among racial/ethnic groups. A total of 412 SP-B alleles were analyzed: 206 from Caucasian, 68 from African-American, and 138 from Nigerian individuals. Twelve groups of alleles (A-L) carrying 3 to 18 motifs were found. The distribution of the 12 alleles in the Caucasian group differs from that found in the Nigerian (p < .001) and African-American (p < .001) populations. The overall distribution of alleles between the African-American and the Nigerian populations were not statistically different. Specific alleles were also present in different proportions among the groups studied. For example, the most common allele (allele E) in all three populations is present at a significantly higher frequency in Caucasians than in the other two populations, but its frequency does not differ from the Nigerian and African-American groups. A less frequent allele, H, also differs significantly when Caucasians are compared with each of the other two populations, but the frequency of this allele is comparable between the African-American and Nigerian populations. To assess the importance of having comparable racial composition between the control and the case groups, a group of African-Americans with respiratory distress syndrome (RDS) (n = 40) was compared with the African American and the Caucasian groups studied above. No significant difference was observed between the racially matched groups but a significant difference (p = .006) was observed between the racially mixed groups. The results indicate that the distribution of SP-B alleles differs between the racial groups but not between the ethnic groups studied. Thus, racial composition of the groups under study is important when considering whether particular alleles at this locus predispose to inherited disorders.

Surfactant protein B gene variations enhance susceptibility to squamous cell carcinoma of the lung in German patients

“…The variability within intron 4 of the surfactant protein B gene is caused by the gain or loss of motifs Veletza et al, 1996), consisting of a 20 bp conserved sequence followed by various dinucleotide repeats (CA-repeats). Currently, it is not known whether the intron 4 variability has an impact on SP-B gene expression or regulation.…”

“…The PCR were performed as hot-start PCR with following cycling conditions: 30 cycles of 948C for 30 s, 598C for 1 min, 728C for 1 min, and a final cycle of 5 min for 728C. As a size marker we used cloned and sequenced intron 4 fragments as described previously Veletza et al, 1996). The PCR-products and the clones were analysed by 1.5% agarose gel electrophoresis and stained with ethidium bromide.…”

“…This large size gene variant is characterised by deletions or insertions Veletza et al, 1996), as shown schematically in Figure 1. The wild type of intron 4 consists of 11 motifs , while the variants result from gain or loss of motifs, consisting of a 20 bp conserved element, followed by a variable number of CA-repeats.…”

Genetic variant characterization in intron 4 of the surfactant protein B gene

“…Genetic variants in intron 4 are in linkage disequilibrium with genotype at a common non-synonymous (Thr131Ile) single nucleotide polymorphism (C1580T, dbSNP reference Rs1130866) (Haataja, et al, 2000). In premature infants, genetic variant alleles have been associated with increased risk for respiratory distress independently, through interaction with alleles of the 2 surfactant protein A genes, and through interaction with race and gender Haataja, et al, 2000;Hallman, 2004;Kala, et al, 1998;Liu, et al, 2003;Makri, et al, 2002;Veletza, et al, 1996). In adults, genetic variants have been associated with increased risk of acute respiratory distress syndrome, chronic obstructive pulmonary disease, interstitial pulmonary fibrosis, and squamous cell carcinoma of the lung Lin, et al, 2000;Seifart, et al, 2002a;Seifart, et al, 2002b).…”

The Importance of Surfactant on the Development of Neonatal Pulmonary Diseases

“…32,33 Some descriptions about the presence of polymorphisms and mutations in genes from the surfactant components are reported in the literature, particularly regarding the SP-B gene, which seems to be associated with RDS, ARDS, and CAP. [34][35][36][37][38][39][40] The inability to produce SP-B is the result of an autosomic recessive disease that leads to a fatal respiratory insufficiency, congenital alveolar proteinosis (CAP), indicating the fundamental role this protein plays in normal pulmonary function. 41 In 1994, Nogee et al 42 demonstrated the existence of a mutation-type frameshift, consisting of the substitution of a nucleotide sequence, GAA, with a single nucleotide, C, on codon 121 of the gene responsible for the production of SP-B.…”