title: C reactive protein and alpha1-antitrypsin: relationship between levels and gene variants.
abstract: The first step in laboratory diagnosis of alpha1-antitrypsin deficiency (AATD) is the determination of alpha1-antitrypsin (AAT) serum levels; these levels in turn are influenced by the inflammatory status. C reactive protein (CRP) has been proposed as a marker of systemic inflammation. Single nucleotide polymorphisms (SNPs) in the CRP gene have been associated with differences in baseline CRP levels. The purpose of this study was to investigate the relationship between CRP and AAT in the AATD diagnostic setting and to verify whether variations in the CRP gene could influence CRP. We determined AAT and CRP levels in 362 consecutive dried blood spot (DBS) samples submitted for AATD diagnosis and genotyped 3 CRP gene SNPs (rs1205, rs3093077, and rs3091244) associated with variations in serum CRP concentrations. To this aim, we developed a method to measure CRP in a DBS with a good correlation with CRP measurement in serum (r2=0.9927). We showed then that systemic inflammatory status parallels increased levels of AAT (80% of subjects with intermediate AATD and a CRP>0.8 mg/dL had an AAT level above the cut-off of 113 mg/dL) and that this increase might mask the presence of AATD variants. No association was detected between CRP levels and the 3 CRP gene polymorphisms. Simultaneous determination of CRP and AAT is useful in the correct diagnosis of heterozygotes carrying intermediate AATD genotypes; their genetic influence on the CRP level is negligible.
authors.affiliation: Center for Diagnosis of Inherited AAT Deficiency, Laboratory of Biochemistry and Genetics, Institute for Respiratory Disease, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ottaviani
authors.forename: Marina
authors.initials: M
authors.lastname: Gorrini
authors.forename: Roberta
authors.initials: R
authors.lastname: Scabini
authors.forename: Zamir
authors.initials: Z
authors.lastname: Kadija
authors.forename: Elena
authors.initials: E
authors.lastname: Paracchini
authors.forename: Francesca
authors.initials: F
authors.lastname: Mariani
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ferrarotti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Luisetti
mesh_terms: D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000235:genetics; D012016:Reference Values; D057170:Translational Research, Biomedical; D000515:alpha 1-Antitrypsin / Q000097:blood* / Q000235:genetics*; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood / Q000175:diagnosis / Q000235:genetics
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D000515:alpha 1-Antitrypsin; D002097:C-Reactive Protein