Disease relevance of SFTPA2

• Therefore, the SP-A and SP-D genes make particularly good candidates to study factors contributing to pulmonary disease etiopathogenesis [1].
• SP-A1 and SP-A2 variants differentially enhance association of Pseudomonas aeruginosa with rat alveolar macrophages [2].
• The results indicated that these SNPs in the collagen region of SP-A2 may be one of the contributing factors to the genetic predisposition to pulmonary tuberculosis [3].
• SNPs in SP-A2 and MBL genes showed significant associations with patients of allergic bronchopulmonary aspergillosis in an Indian population [4].
• The protective role of lung surfactant proteins SP-A, SP-D and MBL in the host defense against both allergic and invasive aspergillosis was identified and established by a series of in vitro and in vivo studies [4].

Psychiatry related information on SFTPA2

• We speculate that this SP-A2 protein, like other serous secretions from airway submucosal glands, functions in local antimicrobial host defense mechanisms in the conducting airways [5].

High impact information on SFTPA2

• We show that certain SP-A1 alleles (6A2 and 6A3) and an SP-A1/SP-A2 haplotype (6A2/1A0) were associated with RDS [6].
• According to the results of conditional logistic-regression analysis, diseases associated with premature birth did not explain the association between the odds of a particular homozygous SP-A1 genotype (6A2/6A2 and 6A3/6A3) and RDS [6].
• Maximal induction of SP-A occurred with 3-10 nM dexamethasone and approximately 300 nM cortisol for 72 hr, and stimulation diminished at higher concentrations [7].
• We propose that glucocorticoids have both stimulatory and inhibitory effects on SP-A gene expression [7].
• When explants were exposed to cortisol for only 24 hr, SP-A content was transiently increased above the level in continuously treated tissue and subsequently was similar to control [7].

Chemical compound and disease context of SFTPA2

• In the lung adenocarcinoma cell line NCI-H441, dexamethasone causes a dose-dependent decrease in total SP-A mRNA levels and inhibits SP-A gene transcription [8].
• Serum SP-A level (n=134) was elevated in acute respiratory distress syndrome and in some cases of drowning, fire and MA fatalities, hyperthermia and chest traumas [9].

Biological context of SFTPA2

• Characterization of two overlapping genomic clones revealed that the SP-A pseudogene lies in a reverse orientation 15 kb away from the 5' side of SP-A1 [10].
• The SP-A and SP-D loci were also oriented relative to the centromere, with the overall order being: centromere-SP-D-SP-A2-pseudogene-SP-A1- telomere [10].
• The relative location of SP-A2 and SP-D was then ascertained by testing a number of sequence tagged sites against the Stanford TNG3 and G3 radiation hybrid panels [10].
• The human surfactant protein (SP) A locus has been assigned to chromosome 10q22-q23 and consists of two very similar genes, SP-A1 and SP-A2, as well as a truncated pseudogene [10].
• Organization of the human SP-A and SP-D loci at 10q22-q23. Physical and radiation hybrid mapping reveal gene order and orientation [10].

Anatomical context of SFTPA2

• Only SP-A2 mRNA was detected in RNA isolated from human fetal trachea and bronchi [11].
• Our results suggest that SP-A2, and not SP-A1, is produced in the human fetal tracheal and bronchial epithelium and in submucosal glands [11].
• Immunohistochemical analysis revealed positive reactivity for SP-A in a subgroup of epithelial cells in the intestine [12].
• We demonstrate that both SP-A genes are expressed in human small and large intestine [12].
• Somatic cell hybrid mapping places the human SP-A and SP-D genes at 10q22-q23 while MBL is localised at 10q21 [13].

Associations of SFTPA2 with chemical compounds

• SP-A2 binds with a higher affinity to a wider variety of sugars than SP-A1 at either 1 or 5 mM Ca(2+) [14].
• All of the SP-A proteins bind to fucose with the greatest affinity [14].
• To explore whether a tryptophan (present in 6A(4)) or an arginine (present in other SP-A1 alleles and in all SP-A2 alleles) at amino acid 219 alters protein behavior, two truncated proteins that varied only at amino acid 219 were oxidized by exposure to ozone [15].
• CONCLUSIONS: Gene polymorphism resulting in the substitution of glutamine with lysine at residue 223 in the carbohydrate recognition domain of SP-A2 increases susceptibility to meningococcal disease, as well as the risk of death [16].
• The region -32/+63 relative to the start of SP-A1 transcription mediated both basal promoter activity and dexamethasone repression of transcription [8].

Other interactions of SFTPA2

• The human SP-A gene locus includes two functional genes, SFTPA1 and SFTPA2 which are expressed independently, and a pseudo gene [17].
• MEASUREMENTS: The SNPs in four exons and intermediate introns of the SP-A1 and SP-A2 were screened by polymerase chain reaction and sequencing [18].
• DNA samples from 441 premature singleton infants and 480 twin or multiple infants were genotyped for surfactant-specific protein (SP)-A1, SP-A2, and SP-B exon 4 polymorphisms and intron 4 size variants in a homogeneous white population [19].
• Competition and supershift EMSA indicate that the ubiquitously expressed transcription factor Sp1, a GC box-binding protein of approximately 100 kDa, is a component of the complex of proteins that bind the GT box of SP-A2 [20].
• A significantly higher frequency of the AGA allele (A1660G) of SP-A2 was observed in patients with ABPA in comparison with control subjects (P =.0156, odds ratio [OR] = 4.78, 95% CI = 1.23 < OR < 18.52) [21].

Analytical, diagnostic and therapeutic context of SFTPA2

• Low-stringency PCR using the SFTP1 primer pair suggested the presence of at least two additional SP-A-related genes in the same region [22].
• SP-A protein was localized by immunocytochemistry to scattered epithelial cells in the airway surface epithelium and in submucosal glands of the fetal trachea and bronchi [11].
• SP-A mRNA (2.2 kb) was detected by Northern blot analysis in human fetal trachea, as well as in primary and more distal bronchi [11].
• SP-A mRNA was localized by in situ hybridization in the fetal trachea and bronchi in scattered cells in the surface epithelium and, most prominently, in submucosal glands [11].
• By UV cross-linking and SDS-PAGE/EMSA analysis, we have identified a approximately 55-kDa GT box-binding factor in type II cell nuclear proteins that preferentially binds the GT box of SP-A2 over the consensus Sp1 GC box sequence [20].

References