Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Dermatology
Published in: BMC Dermatology 1/2014

Open Access 01-12-2014 | Research article

Association of variation in the LAMA3 gene, encoding the alpha-chain of laminin 5, with atopic dermatitis in a German case–control cohort

Authors: Susanne Stemmler, Qumar Parwez, Elisabeth Petrasch-Parwez, Joerg T Epplen, Sabine Hoffjan

Published in: BMC Dermatology | Issue 1/2014

Login to get access

Abstract

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disorder caused by complex interaction of genetic and environmental factors. Besides mutations in the filaggrin gene, leading to impaired skin barrier function, variation in genes encoding additional skin proteins has been suggested to contribute to disease risk. Laminin 5, playing an important role in skin integrity, is composed of three subunits encoded by the LAMA3, LAMB3 and LAMC2 genes in which biallelic mutations cause epidermolysis bullosa junctionalis. We aimed at evaluating the role of variation in the LAMA3, LAMB3 and LAMC2 genes for AD pathogenesis.

Methods

29 single nucleotide polymorphisms (SNPs) were genotyped in the three genes in a German AD case–control cohort comprising 470 unrelated AD patients and 320 non-atopic controls by means of restriction enzyme digestion. Allele, genotype and haplotype frequencies were compared between cases and controls using chi-square testing and the Haploview software.

Results

Several SNPs in the LAMA3 gene showed significant association with AD in our cohort (p <0.01), while we did not detect association with variations in the LAMB3 and LAMC2 genes. Haplotype analysis additionally revealed several significantly associated haplotypes in the LAMA3 gene. Due to extensive linkage disequilibrium, though, we were not able to further differentiate the specific disease causing variation(s) in this region.

Conclusions

We established the LAMA3 gene as novel potential susceptibility gene for AD. Additional studies in independent cohorts are needed to replicate these results.
Appendix
Available only for authorised users
Literature
1.
Holloway JW, Yang IA, Holgate ST: Genetics of allergic disease. J Allergy Clin Immunol 2010, 125: S81-S94. 10.1016/j.jaci.2009.10.071CrossRefPubMed
2.
Boguniewicz M, Leung DY: Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev 2011, 242: 233–246. 10.1111/j.1600-065X.2011.01027.xCrossRefPubMedPubMedCentral
3.
Kypriotou M, Huber M, Hohl D: The human epidermal differentiation complex: cornified envelope precursors, S100 proteins and the ‘fused genes’ family. Exp Dermatol 2012, 21: 643–649. 10.1111/j.1600-0625.2012.01472.xCrossRefPubMed
4.
Irvine AD, McLean WH, Leung DY: Filaggrin mutations associated with skin and allergic diseases. N Engl J Med 2011, 365: 1315–1327. 10.1056/NEJMra1011040CrossRefPubMed
5.
McAleer MA, Irvine AD: The multifunctional role of filaggrin in allergic skin disease. J Allergy Clin Immunol 2013, 131: 280–291. 10.1016/j.jaci.2012.12.668CrossRefPubMed
6.
Jakasa I, Koster ES, Calkoen F, McLean WH, Campbell LE, Bos JD, Verberk MM, Kezic S: Skin barrier function in healthy subjects and patients with atopic dermatitis in relation to filaggrin loss-of-function mutations. J Invest Dermatol 2011, 131: 540–542. 10.1038/jid.2010.307CrossRefPubMed
7.
Nishiyama T, Amano S, Tsunenaga M, Kadoya K, Takeda A, Adachi E, Burgeson RE: The importance of laminin 5 in the dermal-epidermal basement membrane. J Dermatol Sci 2000, 24(Suppl 1):S51-S59.CrossRefPubMed
8.
Schneider H, Muhle C, Pacho F: Biological function of laminin-5 and pathogenic impact of its deficiency. Eur J Cell Biol 2007, 86: 701–717. 10.1016/j.ejcb.2006.07.004CrossRefPubMed
9.
Akutsu N, Amano S, Nishiyama T: Quantitative analysis of laminin 5 gene expression in human keratinocytes. Exp Dermatol 2005, 14: 329–335. 10.1111/j.0906-6705.2005.00275.xCrossRefPubMed
10.
11.
Amano S, Akutsu N, Ogura Y, Nishiyama T: Increase of laminin 5 synthesis in human keratinocytes by acute wound fluid, inflammatory cytokines and growth factors, and lysophospholipids. Br J Dermatol 2004, 151: 961–970. 10.1111/j.1365-2133.2004.06175.xCrossRefPubMed
12.
Macaluso F, Nothnagel M, Parwez Q, Petrasch-Parwez E, Bechara FG, Epplen JT, Hoffjan S: Polymorphisms in NACHT-LRR (NLR) genes in atopic dermatitis. Exp Dermatol 2007, 16: 692–698. 10.1111/j.1600-0625.2007.00589.xCrossRefPubMed
13.
Hanifin JM, Rajka G: Diagnostic features of atopic dermatitis. Acta Derm Venereol 1980, 92: 44–47.
14.
Bel EH: Clinical phenotypes of asthma. Curr Opin Pulm Med 2004, 10: 44–50. 10.1097/00063198-200401000-00008CrossRefPubMed
15.
De Marco R, Locatelli F, Cerveri I, Bugiani M, Marinoni A, Giammanco G: Incidence and remission of asthma: a retrospective study on the natural history of asthma in Italy. J Allergy Clin Immunol 2002, 110: 228–235. 10.1067/mai.2002.125600CrossRefPubMed
16.
Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988, 16: 1215. 10.1093/nar/16.3.1215CrossRefPubMedPubMedCentral
17.
International HapMap Consortium: The International HapMap Project. Nature 2003, 426: 789–796. 10.1038/nature02168CrossRef
18.
19.
Barrett JC: Haploview: Visualization and analysis of SNP genotype data. Cold Spring Harb Protoc 2009, pdb ip71.
20.
Boehringer S, Epplen JT, Krawczak M: Genetic association studies of bronchial asthma–a need for Bonferroni correction? Hum Genet 2000, 107: 197. 10.1007/s004390000353CrossRefPubMed
21.
Menning M, Kufer TA: A role for the Ankyrin repeat containing protein Ankrd17 in Nod1- and Nod2-mediated inflammatory responses. FEBS Lett 2013, 587: 2137–2142. 10.1016/j.febslet.2013.05.037CrossRefPubMed
22.
23.
24.
McLean WH, Irvine AD: Heritable filaggrin disorders: the paradigm of atopic dermatitis. J Invest Dermatol 2012, 132: E20-E21.CrossRefPubMed
25.
De Benedetto A, Rafaels NM, McGirt LY, Ivanov AI, Georas SN, Cheadle C, Berger AE, Zhang K, Vidyasagar S, Yoshida T, Boguniewicz M, Hata T, Schneider LC, Hanifin JM, Gallo RL, Novak N, Weidinger S, Beaty TH, Leung DY, Barnes KC, Beck LA: Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol 2010, 127: 773–786.CrossRefPubMedPubMedCentral
26.
Paternoster L, Standl M, Chen CM, Ramasamy A, Bonnelykke K, Duijts L, Ferreira MA, Alves AC, Thyssen JP, Albrecht E, Baurecht H, Feenstra B, Sleiman PM, Hysi P, Warrington NM, Curjuric I, Myhre R, Curtin JA, Groen-Blokhuis MM, Kerkhof M, Sääf A, Franke A, Ellinghaus D, Fölster-Holst R, Dermitzakis E, Montgomery SB, Prokisch H, Heim K, Hartikainen AL, Pouta A, et al.: Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet 2012, 44: 187–192.CrossRef
27.
Marenholz I, Rivera VA, Esparza-Gordillo J, Bauerfeind A, Lee-Kirsch MA, Ciechanowicz A, Kurek M, Piskackova T, Macek M, Lee YA: Association screening in the Epidermal Differentiation Complex (EDC) identifies an SPRR3 repeat number variant as a risk factor for eczema. J Invest Dermatol 2011, 131: 1644–1649. 10.1038/jid.2011.90CrossRefPubMed
28.
Bergboer JG, Zeeuwen PL, Irvine AD, Weidinger S, Giardina E, Novelli G, Den Heijer M, Rodriguez E, Illig T, Riveira-Munoz E, Campbell LE, Tyson J, Dannhauser EN, O'Regan GM, Galli E, Klopp N, Koppelman GH, Novak N, Estivill X, McLean WH, Postma DS, Armour JA, Schalkwijk J: Deletion of Late Cornified Envelope 3B and 3C genes is not associated with atopic dermatitis. J Invest Dermatol 2010, 130: 2057–2061. 10.1038/jid.2010.88CrossRefPubMed
29.
Bieber T, Cork M, Reitamo S: Atopic dermatitis: a candidate for disease-modifying strategy. Allergy 2012, 67: 969–975. 10.1111/j.1398-9995.2012.02845.xCrossRefPubMed
30.
Heimall J, Spergel JM: Filaggrin mutations and atopy: consequences for future therapeutics. Expert Rev Clin Immunol 2012, 8: 189–197. 10.1586/eci.11.100CrossRefPubMed
Metadata
Title
Association of variation in the LAMA3 gene, encoding the alpha-chain of laminin 5, with atopic dermatitis in a German case–control cohort
Authors
Susanne Stemmler
Qumar Parwez
Elisabeth Petrasch-Parwez
Joerg T Epplen
Sabine Hoffjan
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Dermatology / Issue 1/2014
Electronic ISSN: 1471-5945
DOI
https://doi.org/10.1186/1471-5945-14-17

Other articles of this Issue 1/2014

BMC Dermatology 1/2014 Go to the issue

Research article

Distribution of Malassezia species on the skin of patients with atopic dermatitis, psoriasis, and healthy volunteers assessed by conventional and molecular identification methods

Case report

Tomotherapy concomitant with cetuximab, followed by cetuximab as single-agent therapy for unresectable squamous cell carcinoma of the skin: a case report

Research article

A systematic literature review of pediculosis due to head lice in the Pacific Island Countries and Territories: what country specific research on head lice is needed?

Research article

Exploring patterns of recurrent melanoma in Northeast Scotland to inform the introduction a digital self-examination intervention

Research article

A laboratory-based study on patients with Parkinson’s disease and seborrheic dermatitis: the presence and density of Malassezia yeasts, their different species and enzymes production

Research article

Digital photography in skin cancer screening by mobile units in remote areas of Brazil