Connexin 37 and Connexin 43 genotypes in correlation to cytokines in induced sputum and blood in cystic fibrosis (CF)

  • Aims: We have provided evidence in former studies that cytokines (IL-8, TNF alpha, LBP, TGFß) measured in blood correlate negatively with lung function in deltaF508 homozygous patients. GAP junction proteins might be of importance for the influx of blood cells into the lung. Our aim was to assess the relationship between connexin genotypes and cytokines (IL-8, TNF-alpha, LBP, TGFß) in induced sputum and serum, and lung disease. Methods: 36 patients homozygous for deltaF508 (median age 18 y, m/f 16/20, FEV1(%) 77) were examined. Sequence analysis was performed for genes encoding GAP junction protein alpha 1 (GJA1/connexin 43) and gap junction protein alpha 4 (GJA4/connexin 37). Cytokines were assessed in serum and induced sputum (IS) by chemiluminescence (DPC Biermann, Bad Homburg, Germany) as well as leukocyte counts. Results: DNA analysis was performed in 35 patients. Whereas GJA1 showed only one rare heterozygous synonymous SNP (rs138386744) in one patient, four common SNPs were detected in GJA4. Two were synonymous changes, but the third variant (rs41266431) predicts an amino acid substitution (GTA → valine, ATA → isoleucine) as well as the fourth SNP (rs1764391: CCC→proline, TCC→serine). For rs41266431 patients with homozygosity for the G variant had higher IL-8 levels (median: 13.3/8.0 pg/ml, p=0.07) in serum as well as leukocytes in sputum (median: 2050/421 /µl p=0.041) than those showing heterozygosity (G/A). In individuals > 30 years lung function (FEV1 41.3/84.83 % predicted, p=0.07) was worse. Conclusion: SNP rs41266431 seems a promising candidate for further investigations, suggesting GJA4 a potential disease modifying gene.

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Author:Michael Ludwig, Olaf EickmeierORCiDGND, Christina Smaczny, Felix Schreiner, Wilma Dubois, Doris N'Gampolo, Ralf SchubertORCiDGND, Stefan ZielenORCiDGND, Ralf Ganschow, Sabina Schmitt-Grohé
Parent Title (English):Molecular and Cellular Pediatrics
Publisher:Springer Open
Place of publication:Berlin ; Heidelberg [u. a.]
Document Type:Conference Proceeding
Year of Completion:2014
Date of first Publication:2014/09/11
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:50th Workshop for Pediatric Research, Gottingen, Germany. 20-21 March 2014
Release Date:2014/10/28
Issue:(Suppl 1):A11
Page Number:1
First Page:1
Last Page:1
© 2014 Ludwig et al; licensee Springer This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Institutes:Medizin / Medizin
Fachübergreifende Einrichtungen / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES)
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 2.0