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Relevance of α-defensins (HNP1-3) and defensin β-1 in diabetes.
World J Gastroenterol 2014; 20(27):9128-37WJ

Abstract

AIM

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%).

CONCLUSION

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+Show Affiliations

Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.Balázs Csaba Németh, Ferenc Somogyvári, Yvette Mándi, Department of Medical Microbiology and Immunology, University of Szeged, H-6720 Szeged, Hungary.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25083086

Citation

Németh, Balázs Csaba, et al. "Relevance of Α-defensins (HNP1-3) and Defensin Β-1 in Diabetes." World Journal of Gastroenterology, vol. 20, no. 27, 2014, pp. 9128-37.
Németh BC, Várkonyi T, Somogyvári F, et al. Relevance of α-defensins (HNP1-3) and defensin β-1 in diabetes. World J Gastroenterol. 2014;20(27):9128-37.
Németh, B. C., Várkonyi, T., Somogyvári, F., Lengyel, C., Fehértemplomi, K., Nyiraty, S., ... Mándi, Y. (2014). Relevance of α-defensins (HNP1-3) and defensin β-1 in diabetes. World Journal of Gastroenterology, 20(27), pp. 9128-37. doi:10.3748/wjg.v20.i27.9128.
Németh BC, et al. Relevance of Α-defensins (HNP1-3) and Defensin Β-1 in Diabetes. World J Gastroenterol. 2014 Jul 21;20(27):9128-37. PubMed PMID: 25083086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relevance of α-defensins (HNP1-3) and defensin β-1 in diabetes. AU - Németh,Balázs Csaba, AU - Várkonyi,Tamás, AU - Somogyvári,Ferenc, AU - Lengyel,Csaba, AU - Fehértemplomi,Katalin, AU - Nyiraty,Szabolcs, AU - Kempler,Péter, AU - Mándi,Yvette, PY - 2013/12/10/received PY - 2014/02/07/revised PY - 2014/04/08/accepted PY - 2014/8/2/entrez PY - 2014/8/2/pubmed PY - 2015/4/18/medline KW - Copy number polymorphism KW - Diabetes KW - HNP1-3 KW - Single nucleotide polymorphism KW - α-defensins KW - β-defensin 1 SP - 9128 EP - 37 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 20 IS - 27 N2 - AIM: 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%). CONCLUSION: 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. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/25083086/Relevance_of_α_defensins__HNP1_3__and_defensin_β_1_in_diabetes_ L2 - http://www.wjgnet.com/1007-9327/full/v20/i27/9128.htm DB - PRIME DP - Unbound Medicine ER -