Feasibility of establishing deletion of the late cornified envelope genes LCE3B and LCE3C as a susceptibility factor for psoriasis

Authors
Safia Bashir 1
Iffat Hassan 1
Sabhiya Majid 2
Yasmeen Jabeen Bhat 1
Rabia Farooq 2
1 Department of Dermatology, Sexually Transmitted Diseases and Leprosy, Government Medical College Srinagar, University of Kashmir, Jammu and Kashmir, India
2 Department of Biochemistry, Government Medical College Srinagar, University of Kashmir, Jammu and Kashmir, India
Abstract
Background: Psoriasis is a chronic hyperproliferative inflammatory disease of the skin, genetic predisposition to which is well-established. The late cornified envelope genes LCE3B and LCE3C are involved in maintaining the integrity of skin barrier especially following skin barrier disruption. The deletion of these genes would lead to an impaired epidermal response following damage to the skin barrier thus predisposing to psoriatic lesions. This study aimed to evaluate the common deletion of late cornified envelope genes (LCE 3B/3C) in psoriasis patients of Kashmiri ethnic population of North India.
Materials and Methods: It was a hospital-based, case-control study which included 100 psoriasis cases and an equal number of controls. Blood samples were obtained, and DNA was extracted from all the samples by a kit-based method. To determine the LCE3C_LCE3B-del genotype, a three-primer polymerase chain reaction assay was performed.




Results: The genotype for the common LCE3C_LCE3B deletion in 100 psoriasis patients and 100 controls was determined. Among the cases, 17 cases were homozygous for insertion genotype (I/I), 40 cases were heterozygous for insertion/deletion genotype (I/D) and 43 cases were homozygous for deletion genotype (D/D), compared to controls where 20 cases were homozygous for insertion genotype (I/I), 45 cases were heterozygous for insertion/deletion genotype (I/D), and 35 cases were homozygous for deletion genotype (D/D). The del/del frequency was higher among psoriatic patients compared to controls (43% vs. 35%) although the difference was not statistically significant (P = 0.507).
Conclusion: We hereby infer that LCE3C_LCE3B deletion does not appear to be associated with the risk of psoriasis in our population.

Keywords

1.
Nevitt GJ, Hutchinson PE. Psoriasis in the community: Prevalence, severity and patients' beliefs and attitudes towards the disease. Br J Dermatol 1996;135:533-7.  Back to cited text no. 1
    
2.
Schon MP, Boehncke WH. Psoriasis. N Engl J Med 2005;352:899-912.  Back to cited text no. 2
    
3.
Masood Q, Hassan I. Pattern of skin disorders in Kashmir Valley. Indian J Dermatol 2002;47:147-8.  Back to cited text no. 3
  Medknow Journal  
4.
Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 2007;80:273-90.  Back to cited text no. 4
    
5.
Capon F, Bijlmakers MJ, Wolf N, Quaranta M, Huffmeier U, Allen M, et al. Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. Hum Mol Genet 2008;17:1938-45.  Back to cited text no. 5
    
6.
Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 2009;41:199-204.  Back to cited text no. 6
[PUBMED]    
7.
Zhang XJ, Huang W, Yang S, Sun LD, Zhang FY, Zhu QX, et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 2009;41:205-10.  Back to cited text no. 7
    
8.
Stuart PE, Nair RP, Ellinghaus E, Ding J, Tejasvi T, Gudjonsson JE, et al. Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet 2010;42:1000-4.  Back to cited text no. 8
    
9.
Sun LD, Cheng H, Wang ZX, Zhang AP, Wang PG, Xu JH, et al. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet 2010;42:1005-9.  Back to cited text no. 9
    
10.
Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium, Strange A, Capon F, Spencer CC, Knight J, Weale ME, et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 2010;42:985-90.  Back to cited text no. 10
    
11.
Ellinghaus E, Ellinghaus D, Stuart PE, Nair RP, Debrus S, Raelson JV, et al. Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet 2010;42:991-5.  Back to cited text no. 11
    
12.
Ellinghaus D, Ellinghaus E, Nair RP, Stuart PE, Esko T, Metspalu A, et al. Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci. Am J Hum Genet 2012;90:636-47.  Back to cited text no. 12
    
13.
Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE, Capon F, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet 2012;44:1341-8.  Back to cited text no. 13
[PUBMED]    
14.
Coto E, Santos-Juanes J, Coto-Segura P, Díaz M, Soto J, Queiro R, et al. Mutation analysis of the LCE3B/LCE3C genes in Psoriasis. BMC Med Genet 2010;11:45.  Back to cited text no. 14
    
15.
Hüffmeier U, Bergboer JG, Becker T, Armour JA, Traupe H, Estivill X, et al. Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors. J Invest Dermatol 2010;130:979-84.  Back to cited text no. 15
    
16.
Xu L, Li Y, Zhang X, Sun H, Sun D, Jia X, et al. Deletion of LCE3C and LCE3B genes is associated with psoriasis in a Northern Chinese population. Br J Dermatol 2011;165:882-7.  Back to cited text no. 16
    
17.
Li M, Wu Y, Chen G, Yang Y, Zhou D, Zhang Z, et al. Deletion of the late cornified envelope genes LCE3C and LCE3B is associated with psoriasis in a Chinese population. J Invest Dermatol 2011;131:1639-43.  Back to cited text no. 17
    
18.
Bergboer JG, Zeeuwen PL, Schalkwijk J. Pathogenesis of atopic dermatitis and psoriasis: Focus on the epidermal differentiation complex. Open Dermatol J 2010;4:48-51.  Back to cited text no. 18
    
19.
de Cid R, Riveira-Munoz E, Zeeuwen PL, Robarge J, Liao W, Dannhauser EN, et al. Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nat Genet 2009;41:211-5.  Back to cited text no. 19
    
20.
Andressen C, Henseler T. Inheritance of psoriasis. Analysis of 2035 family histories. Hautarzt 1982;33:214-7.  Back to cited text no. 20
[PUBMED]    
21.
De Benedetto A, Kubo A, Beck LA. Skin barrier disruption: A requirement for allergen sensitization? J Invest Dermatol 2012;132(3 Pt 2):949-63.  Back to cited text no. 21
    
22.
Raychaudhuri SP, Farber EM. The prevalence of psoriasis in the world. J Eur Acad Dermatol Venereol 2001;15:16-7.  Back to cited text no. 22
    
23.
Okhandiar RP, Banerjee BN. Psoriasis in the tropics: An epidemiological survey. J Indian Med Assoc 1963;41:550-6.  Back to cited text no. 23
[PUBMED]    
24.
Bedi TR. Psoriasis in North India. Geographical variations. Dermatologica 1977;155:310-4.  Back to cited text no. 24
[PUBMED]    
25.
Bedi TR. Clinical profile of psoriasis in North India. Indian J Dermatol Venereol Leprol 1995;61:202-5.  Back to cited text no. 25
[PUBMED]  Medknow Journal  
26.
Kaur I, Handa S, Kumar B. Natural history of psoriasis: A study from the Indian subcontinent. J Dermatol 1997;24:230-4.  Back to cited text no. 26
    
27.
Henseler T, Christophers E. Psoriasis of early and late onset: Characterization of two types of psoriasis vulgaris. J Am Acad Dermatol 1985;13:450-6.  Back to cited text no. 27
[PUBMED]    
28.
Henseler T. The genetics of psoriasis. J Am Acad Dermatol 1997;37(2 Pt 3):S1-11.  Back to cited text no. 28
    
29.
Farber EM, Nall ML. The natural history of psoriasis in 5,600 patients. Dermatologica 1974;148:1-18.  Back to cited text no. 29
[PUBMED]    
30.
Ammar M, Bouchlaka-Souissi C, Soumaya K, Bouhaha R, Ines Z, Bouazizi F, et al. Failure to find evidence for deletion of LCE3C and LCE3B genes at PSORS4 contributing to psoriasis susceptibility in Tunisian families. Pathol Biol (Paris) 2014;62:34-7.  Back to cited text no. 30
    
31.
Wiwanitkit V. LCE3C_LCE3B-del genotype and psoriasis: A summative meta-analysis. Acta Dermatovenerol Croat 2010;18:130.  Back to cited text no. 31
[PUBMED]    
32.
Song GG, Kim JH, Lee YH. Association between the LCE3C_LCE3B deletion polymorphism and susceptibility to psoriasis: A meta-analysis of published studies. Genet Test Mol Biomarkers 2013;17:572-7.  Back to cited text no. 32
    
33.
Ammar M, Bouazizi F, Bouhaha R, Zaraa I, Kouidhi S, Ourheni S, et al. Association analysis of LCE3C-LCE3B deletion in Tunisian psoriatic population. Arch Dermatol Res 2012;304:733-8.  Back to cited text no. 33
    
34.
Jackson B, Tilli CM, Hardman MJ, Avilion AA, MacLeod MC, Ashcroft GS, et al. Late cornified envelope family in differentiating epithelia – Response to calcium and ultraviolet irradiation. J Invest Dermatol 2005;124:1062-70.  Back to cited text no. 34
Advanced Biomedical Research
Volume 2016, june
June 2016
Pages 1-6