Association of polymorphisms in the collagen region of SP-A2 with increased levels of total IgE antibodies and eosinophilia in patients with allergic bronchopulmonary aspergillosis.
BACKGROUND
Studies from our group have shown a protective role of pulmonary surfactant protein A (SP-A) against lung allergy and infections caused by Aspergillus fumigatus.


OBJECTIVE
Present study investigated the association of polymorphisms in the collagen region of SP-A1 and SP-A2 (genes encoding SP-A) with allergic bronchopulmonary aspergillosis (ABPA) and its clinical markers.


METHODS
Genomic DNA was extracted from blood samples of patients with ABPA and age-matched, unrelated control subjects. The polymorphisms were detected by means of PCR amplification and sequencing of the collagen region of SP-A1 and SP-A2.


RESULTS
Two exonic (SP-A2 G1649C and SP-A2 A1660G, 10 patients and 11 control subjects) and 2 intronic (SP-A2 T1492C, 8 patients and 8 control subjects; SP-A1 C1416T, 5 patients and 7 control subjects) polymorphisms in the collagen region of SP-A2 and SP-A1 showed significant association with patients with ABPA. 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). This polymorphism, when existing along with a nonredundant polymorphism, SP-A2 G1649C (Ala91Pro) resulted in a stronger association with ABPA (A1660G and G1649C: P =.0079, OR = 10.4, 95% CI = 1.62 < OR < 66.90). Patients with ABPA with GCT and AGG alleles showed significantly high levels of total IgE and percentage eosinophilia versus patients with ABPA with CCT and AGA alleles.


CONCLUSIONS
The results indicated that SP-A2 G1649C and SP-A2 A1660G, polymorphisms in the collagen region of SP-A2, might be one of the contributing factors to genetic predisposition and severity of clinical markers of ABPA.
Saxena
Shweta
S
Molecular Biochemistry and Diagnostics Division, Institute of Genomics and Integrative Biology, Delhi, India.
Madan
Taruna
T
Shah
Ashok
A
Muralidhar
Kambadur
K
Sarma
Puranam Usha
PU
D000293:Adolescent; D000328:Adult; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000235:genetics* / Q000276:immunology; D002648:Child; D003094:Collagen / Q000235:genetics*; D004802:Eosinophilia / Q000209:etiology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D037662:Pulmonary Surfactant-Associated Protein A / Q000031:analogs & derivatives* / Q000235:genetics*
D037662:Pulmonary Surfactant-Associated Protein A; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human; D007073:Immunoglobulin E; D003094:Collagen