Development of novel microarray methodology for the study of mutations in the SERPINA1 and ADRB2 genes--their association with Obstructive Pulmonary Disease and Disseminated Bronchiectasis in Greek patients.
OBJECTIVE
The aim of our study was to determine the genetic risk conferred by SNPs in the SERPINA1 and ADRB2 for development of Chronic Obstructive Pulmonary Disease (COPD) and Disseminated Bronchiectasis (DB), while at the same time validating the NanoChip technology. This was a case-control study consisting of 112 COPD, 62 DB patients and 2 control groups (106 smokers without COPD: healthy smokers control group and 205 general population subjects).


METHODS
The novel methodology of the Nanogen NanoChip(R) 400 (NC400 Nanogen www.nanogen.com) was employed for genotyping five mutations/SNPs in the SERPINA1 and 2 in the ADRB2 gene.


RESULTS
For the SERPINA1 gene a statistically significant difference in the frequency was found for heterozygotes for p.V213A between DB patients and healthy smokers (44.1% vs. 26.4% respectively; p=0.035) and for heterozygotes for c.1237G>A between DB patients and general population subjects (10.2% vs. 25.4% respectively; p=0.023). There was a clustering of ADRB2 p.Gly16 homozygotes in patients with severe COPD (24/44, 54.5% with FEV(1) values <35% of predicted).


CONCLUSIONS
The SERPINA1 p.V213A polymorphism was found associated with DB risk while the ADRB2 p.G16R is a risk factor for severe COPD in smokers.
Papatheodorou
Athanasios
A
Department of Medical Genetics, Medical School, University of Athens, Thivon and Levadias, 11257 Athens, Greece. atpapath@med.uoa.gr
Makrythanasis
Periklis
P
Kaliakatsos
Marios
M
Dimakou
Aikaterini
A
Orfanidou
Dora
D
Roussos
Charis
C
Kanavakis
Emmanuel
E
Tzetis
Maria
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001987:Bronchiectasis / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006115:Greece; D006801:Humans; D008297:Male; D046228:Microarray Analysis / Q000379:methods*; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2; C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin