Indian Journal of Dermatology
  Publication of IADVL, WB
  Official organ of AADV
Indexed with Science Citation Index (E) , Web of Science and PubMed
 
Users online: 3023  
Home About  Editorial Board  Current Issue Archives Online Early Coming Soon Guidelines Subscriptions  e-Alerts    Login  
    Small font sizeDefault font sizeIncrease font size Print this page Email this page


 
Table of Contents 
CORRESPONDENCE
Year : 2022  |  Volume : 67  |  Issue : 3  |  Page : 293-295
Lack of association between CARD11 and atopic dermatitis in Chinese population


Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China

Date of Web Publication22-Sep-2022

Correspondence Address:
Furen Zhang
Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_405_19

Rights and Permissions



How to cite this article:
Shi W, Liu H, Yu Y, Wang C, Wang Z, Sun L, Zhang F. Lack of association between CARD11 and atopic dermatitis in Chinese population. Indian J Dermatol 2022;67:293-5

How to cite this URL:
Shi W, Liu H, Yu Y, Wang C, Wang Z, Sun L, Zhang F. Lack of association between CARD11 and atopic dermatitis in Chinese population. Indian J Dermatol [serial online] 2022 [cited 2022 Sep 29];67:293-5. Available from: https://www.e-ijd.org/text.asp?2022/67/3/293/356733




Sir,

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by chronic eczematous skin with inflammation and palindromia. It is described with a defect in skin barrier functions, cutaneous inflammatory hypersensitivity, and antimicrobial immune defense associated with genetic factors.[1],[2] Host genetic factors have been implicated in the pathogenesis of AD by a great amount of association studies. A series of susceptibility genes, such as FLG, C11orf30, TMEM232-SLC25A46, TNFRSF6B-ZGPAT, OVOL1, ACTL9, and KIF3A-IL134-6[3],[4],[5],[6],[7],[8] have been reported to be associated with AD in Chinese, European, and Japanese populations;[3],[5],[6],[8] however, apart from FLG, few of them were found to be overlapped in different populations, which showed the differential effect of these genes in regulating genetic susceptibility to AD. Recently, Chi et al.[9] reported that four germline hypomorphic mutations of CARD11 were associated with atopic disease with increased IgE and eosinophilia in Americans. And also Hirota et al. identified CARD11 to be associated with AD in the Japanese.[8] Herein, we sought to verify whether there is any genetic association between CARD11 with AD patients of Chinese descent.

A total of 118 AD patients were enrolled in the analysis, with 50.8% males and 49.2% females. The mean age was 8.84 ± 6.13 years, and the mean age of onset was 1.87 ± 2.40 years. All AD patients were diagnosed based on the diagnostic criteria proposed by Hanifin and Rajka.[10],[11] Among them, 13 patients suffered from the severe atopic disease who had significantly increased level of IgE and eosinophilia. A total of 94 patients had a family history of atopic disease. Whereas, 72 healthy subjects were recruited as controls, including 40 males and 32 females. The mean age was 22.14 ± 0.88 years. In regards age andgender, the patients and controls were matched. [Table 1] listed the baseline information of all the subjects.
Table 1: Information of subjects

Click here to view


We performed direct DNA sequencing to investigate the prevalence of CARD11 variants in 118 AD patients and 72 healthy controls. Comparing with the control group, only one splice region variant (c.1017 + 3G > A) [Figure 1] was found in one patient without statistical difference (P > 0.05). The mutation was possibly damaging analyzed by the sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen). And, no other nonsynonymous mutations were found in the control group. Four foregone mutations previously reported in Americans[9] were not detected in all the patients.
Figure 1: The splice region variant (c.1017 + 3G > A) sequence of CARD11. Red arrow showed the position of the variant

Click here to view


The pathogenesis of AD is defects in humoral immune responses, involving selective deficits in B-cell activation by antigen receptors and T-cell costimulation by CD28, and gradual development of AD with hyper-IgE. Mutant B-cells are specifically defective in forming connections between antigen receptors and two key signaling pathways for immunogenic responses – NF-κB and ERK.[12] CARD11 was previously reported to be specifically expressed in lymphocytes, it encodes a membrane-associated guanylate kinase (MAGUK)-family protein, and CARD11-BCL10-MALT1 (CBM) signalosome complex, which is required for NF-κB activation by T-cell receptor (TCR) and B-cell receptor (BCR) signaling.[13],[14] Phosphorylation of the linker region of CARD11 is related to induce a conformational change within the CARD11 molecule, allowing the recruitment of BCL10 to CARD11. CARD11 induces BCL10 to oligomerize into helical filamentous structures, which form a platform for the downstream signaling events of the CBM complex, inducing NF-κB activation in receptor signaling pathways.

However, in this study, we failed to find any suggestive associations between CARD11 and AD patients in the Chinese population. One possible cause is that the differences in ethnic lines might be to contribute to this result. In addition, only limited samples were available. Especially, only 13 severe AD were recruited. And more samples are needed to explore the correlation between CARD11 and AD in the Chinese population.

In conclusion, we invested the relationship between the CARD11 gene and 118 AD patients of Chinese descent, and no significant association was found. Further studies should be conducted to reach out a more reliable conclusion.

Financial support and sponsorship

This work was funded by grants from the National Key Research and Development Program of China (2016YFE0201500), the National Natural Science Foundation of China (81822038, 81874244, 81811530342), the Natural Science Foundation of Shandong Province (JQ201616, ZR2018BC020), and the Innovation Project of Shandong Academy of Medical Science.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Bieber T. Mechanisms of disease: Atopic dermatitis. N Engl J Med 2008;358:1483-94.  Back to cited text no. 1
    
2.
Boguniewicz M, Leung DYM. Recent insights into atopic dermatitis and implications for management of infectious complications. J Allergy Clin Immunol 2010;125:4-13.  Back to cited text no. 2
    
3.
Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006;38:441-6.  Back to cited text no. 3
    
4.
Esparza-Gordillo J, Weidinger S, Fölster-Holst R, Bauerfeind A, Ruschendorf F, Patone G. A common variant on chromosome 11q13 is associated with atopic dermatitis. Nat Genet 2009;41:596-601.  Back to cited text no. 4
    
5.
Sun LD, Xiao FL, Li Y, Zhou WM, Tang HY, Tang XF. Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. Nat Genet 2001;43:690-4.  Back to cited text no. 5
    
6.
Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med 2001;365:1315-27.  Back to cited text no. 6
    
7.
Paternoster L, Standl M, Chen CM, Ramasamy A, Bønnelykke K, Duijts L. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat Genet 2012;44:187-92.  Back to cited text no. 7
    
8.
Hirota T, Takahashi A, Kubo M, Tsunoda T, Tomita K, Sakashita M, et al. Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat Genet 2012;44:1222-6.  Back to cited text no. 8
    
9.
Chi AM, Jeffrey RS, Yuan Z, Jordan KA, Michael AW, Pia JH, et al. Germline hypomorphic CARD11 mutations in severe atopic disease. Nat Genet 2017;49:1192-201.  Back to cited text no. 9
    
10.
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm 1980;92:44-7.  Back to cited text no. 10
    
11.
Baron SE, Cohen SN, Archer CB. Guidance on the diagnosis and clinical management of atopic eczema. Clin Exp Dermatol 2012;37(Suppl 1):7-12.  Back to cited text no. 11
    
12.
Jun JE, Wilson LE, Vinuesa CG, Lesage S, Blery M, Miosge LA. Identifying the MAGUK protein Carma-1 as a central regulator of humoral immune responses and atopy by genome-wide mouse mutagenesis. Immunity 2003;18:751-62.  Back to cited text no. 12
    
13.
Turvey SE, Durandy A, Fischer A, Fung SY, Geha RS, Gewies A. The CARD11-BCL10-MALT1 (CBM) signalosome complex: Stepping into the limelight of human primary immunodeficiency. J Allergy Clin Immunol 2014;134:276-84.  Back to cited text no. 13
    
14.
Snow AL, Xiao W, Stinson JR, Lu W, Chaigne-Delalande B, Zheng L, et al. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. J Exp Med 2012;209:2247-61.  Back to cited text no. 14
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1]



 

Top
Print this article  Email this article
 
 
  Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (1,817 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed122    
    Printed2    
    Emailed0    
    PDF Downloaded8    
    Comments [Add]    

Recommend this journal