title: Relevance of α-defensins (HNP1-3) and defensin β-1 in diabetes.
abstract: OBJECTIVE
  To investigate the genetic background of human defensin expression in type 1 and 2 diabetes.
  
  
  METHODS
  Associations between DEFA1/DEFA3 gene copy number polymorphism and diabetes as well as between the promoter polymorphisms of DEFB1 and diabetes were studied. The copy number variation of the DEFA1/DEFA3 genes was determined in 257 diabetic patients (117 patients with type 1 and 140 with type 2 diabetes). The control group consisted of 221 age- and gender-matched healthy blood donors. The cumulative copy numbers of the DEFA1/DEFA3 genes were detected by using quantitative PCR analysis. To evaluate the HNP 1-3 (human neutrophil peptide 1-3 or α-defensin) levels in the circulation, plasma HNP 1-3 concentrations were measured by ELISA. The expression of DEFA1/A3 in peripheral leukocytes of the diabetic patients was measured by quantitative RT PCR analysis. Three SNPs of the human DEFB1 (human defensin β-1) gene: DEFB1 G-20A (rs11362), DEFB1 C-44G (rs1800972) and DEFB1 G-52A (rs1799946) were genotyped by Custom TaqMan(®) Real Time PCR assay.
  
  
  RESULTS
  Significant differences were observed in HNP1-3 levels between the healthy subjects and both groups of diabetic patients. The mean ± SE was 28.78 ± 4.2 ng/mL in type 1 diabetes, and 29.82 ± 5.36 ng/mL in type 2 diabetes, vs 11.94 ± 2.96 ng/mL in controls; P < 0.01 respectively. There was no significant difference between patients with type 1 and type 2 diabetes in the high plasma concentrations of HNP1-3. The highest concentrations of α-defensin were found in diabetic patients with nephropathy (49.4 ± 4.8 ng/mL), neuropathy (38.7 ± 4.8 ng/mL) or cardiovascular complications (45.6 ± 1.45 ng/L). There was no significant difference in the cumulative copy numbers of DEFA1/DEFA3 genes between controls and patients, or between patients with the two types of diabetes. Comparisons of HNP 1-3 plasma level and DEFA1/A3 copy number of the same patient did not reveal significant relationship between defensin-α levels and the gene copy numbers (r (2) = 0.01). Similarly, no positive correlation was observed between the copy numbers and the mRNA expression levels of DEFA1/A3. Regarding the C-44G polymorphism of DEFB1, the GG "protective" genotype was much less frequent (1%-2%) among both groups of patients than among controls (9%).
  
  
  CONCLUSIONS
  Elevated HNP1-3 levels in diabetes are independent of DEFA1/DEFA3 copy numbers, but GG genotype of C-44G SNP in DEFB1 gene may result in decreased defensin β-1 production.
authors.affiliation: Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.
authors.forename: Balázs Csaba
authors.initials: BC
authors.lastname: Németh
authors.affiliation: Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Várkonyi
authors.affiliation: Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Somogyvári
authors.affiliation: Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Lengyel
authors.affiliation: Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Fehértemplomi
authors.affiliation: Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Nyiraty
authors.affiliation: Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Kempler
authors.affiliation: Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Mándi
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D023084:alpha-Defensins / Q000097:blood / Q000235:genetics*; D023083:beta-Defensins / Q000097:blood / Q000235:genetics*
chemical_list: C406407:DEFB1 protein, human; D012333:RNA, Messenger; D023084:alpha-Defensins; D023083:beta-Defensins; C406413:human neutrophil peptide 1; C406427:human neutrophil peptide 3
keywords: Copy number polymorphism; Diabetes; HNP1-3; Single nucleotide polymorphism; α-defensins; β-defensin 1
references.citation: Curr Protein Pept Sci. 2005 Feb;6(1):35-51
references.pmid: 15638767
references.citation: J Pathol. 1998 Sep;186(1):99-103
references.pmid: 9875146
references.citation: Int Arch Allergy Immunol. 2007;142(3):211-8
references.pmid: 17108702
references.citation: J Intern Med. 2003 Sep;254(3):197-215
references.pmid: 12930229
references.citation: Immunol Rev. 2000 Oct;177:68-78
references.pmid: 11138786
references.citation: Genomics. 2005 Oct;86(4):423-30
references.pmid: 16039093
references.citation: Eur J Clin Invest. 2003 Jan;33(1):82-7
references.pmid: 12492457
references.citation: Curr Opin Immunol. 2005 Aug;17(4):359-65
references.pmid: 15955682
references.citation: Hum Mol Genet. 2009 Apr 15;18(R1):R1-8
references.pmid: 19297395
references.citation: Nat Immunol. 2005 Jun;6(6):551-7
references.pmid: 15908936
references.citation: Trends Immunol. 2009 Nov;30(11):513-21
references.pmid: 19699684
references.citation: Peptides. 2006 Apr;27(4):931-40
references.pmid: 16226346
references.citation: FEBS Lett. 1996 Nov 4;396(2-3):319-22
references.pmid: 8915011
references.citation: Autoimmunity. 2009 Aug;42(5):406-13
references.pmid: 19811257
references.citation: Biochem Biophys Res Commun. 2008 Mar 7;367(2):452-6
references.pmid: 18178160
references.citation: Nat Rev Immunol. 2003 Sep;3(9):710-20
references.pmid: 12949495
references.citation: Cancer Res. 2006 Sep 1;66(17):8542-9
references.pmid: 16951166
references.citation: Immunology. 2002 Aug;106(4):517-25
references.pmid: 12153515
references.citation: Infect Immun. 1987 Mar;55(3):568-71
references.pmid: 3643886
references.citation: Am J Physiol Heart Circ Physiol. 2008 Nov;295(5):H1817-24
references.pmid: 18805897
references.citation: J Clin Microbiol. 2003 Jan;41(1):90-6
references.pmid: 12517831
references.citation: Mol Immunol. 2007 Feb;44(5):796-802
references.pmid: 16740310
references.citation: Biotechnol Lett. 2005 Sep;27(18):1337-47
references.pmid: 16215847
references.citation: Trends Immunol. 2002 Jun;23(6):291-6
references.pmid: 12072367
references.citation: Anesthesiology. 2010 Jun;112(6):1428-34
references.pmid: 20502117
references.citation: Nephrol Dial Transplant. 2008 Mar;23(3):914-8
references.pmid: 18003664
references.citation: Cell Immunol. 2012;273(2):158-63
references.pmid: 22248881
references.citation: Genome Res. 2008 Nov;18(11):1686-97
references.pmid: 18974263
references.citation: Cell Mol Life Sci. 2006 Jun;63(11):1294-313
references.pmid: 16710608
references.citation: Infect Immun. 2002 Dec;70(12):6515-7
references.pmid: 12438319
references.citation: Infect Genet Evol. 2009 Jul;9(4):617-25
references.pmid: 19460328
references.citation: FEBS Lett. 2013 Jul 11;587(14):2241-6
references.pmid: 23735697
references.citation: Hum Mol Genet. 2005 Jul 15;14(14):2045-52
references.pmid: 15944200
references.citation: J Clin Endocrinol Metab. 2008 Apr;93(4):1470-5
references.pmid: 18211979
references.citation: Mol Cell Probes. 1998 Jun;12(3):171-3
references.pmid: 9664579