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Commentary
89 (
6
); 795-796
doi:
10.25259/IJDVL_1055_2023
pmid:
37067103

Exploring filaggrin gene polymorphisms in Indian children with atopic dermatitis: Hitherto an unchartered territory

Department of Dermatology, AIIMS, New Delhi, India
Corresponding author: Dr. Riti Bhatia, Department of Dermatology , AIIMS, New Delhi, India. ritibhatia_aiims@yahoo.com
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Bhatia R, Gupta V. Exploring filaggrin gene polymorphisms in Indian children with atopic dermatitis: Hitherto an unchartered territory. Indian J Dermatol Venereol Leprol 2023;89:795-6.

Atopic dermatitis is a chronic, remitting, relapsing inflammatory skin disease caused by a complex interplay of myriad factors, including genetic and epigenetic factors, immune dysregulation, and altered skin microbiome. Loss-of-function mutations in filaggrin (FLG) are associated with a three-to-fourfold increased risk of atopic dermatitis.

In this issue of IJDVL, Srinivas et al. studied FLG gene polymorphisms in 75 Indian children with atopic dermatitis and attempted a genotype-phenotype correlation.1 They found 20 FLG loss of function variants in 34.7% of children. FLG polymorphisms were associated with early-onset of disease and raised serum IgE levels. Similar phenotypic associations with FLG polymorphisms have been recorded by others as well, particularly in Eastern Asian and European populations.2

We know that there are distinct differences between the immunological endotypes of atopic dermatitis in the Asian and European populations, which also explains the differences in their phenotypes.3 Similarly, the prevalence of FLG gene polymorphism prevalence varies between different populations, with its prevalence in European, American, Asian, and African-American patients with atopic dermatitis being 50%, 31.5%, 27%, and 15.3%, respectively.4 The specific FLG variants also differ; the most common variants being R501X, 2282del4, S3247X, and R2447X in European patients; S2889X in patients from the Indian subcontinent; 3321delA in East Asian patients; K4022X in Korean and Northern Chinese patients; and S2554X, S2889X, S3296X, and Q1701X in Japanese patients.2 More variety of FLG polymorphisms was found in populations of Japan, China, Singapore, and Taiwan than of European countries. Of the 20 FLG variants detected by Srinivas et al., 16 (80%) were novel thereby expanding the known spectrum of FLG polymorphisms.1

The importance of the study by Srinivas et al. lies in providing us data that is are unique to the Indian population. India is home to more than 2,000 ethnic populations whose genetic origins are heterogeneous and complex. Surprisingly, there has been a dearth of genomic studies from the Indian subcontinent. Recently, another Indian study from Karnataka found FLG polymorphisms in 28 out of 30 children with atopic dermatitis.5 Of the 22 mutations identified, 17 had not been reported so far.5 Sequencing of the entire FLG gene allowed identification of novel FLG polymorphisms; this was a lacuna in an older earlier study by Handa et al. that focussed on known common FLG variants in chronic hand eczema.6

Genetic studies are much needed in the Indian context, highlighting a difference in the gene pool from other populations. However, the results need to be confirmed on in larger samples, preferably nation-wide multicentric studies. More research is needed to understand how FLG polymorphisms influence the severity and natural course of atopic dermatitis, its associations with other atopic conditions, and its response to treatment. Clinical significance of these novel FLG variants is yet to be determined. Further, as we move into the era of more refined molecular diagnostics (‘omics’), integrating the vast amounts of new information on genetics, epigenomics, proteomics and transcriptomics will allow us to gather a holistic view and deliver a personalized medicine approach to our patients.

Declaration of patient consent

Patient’s consent not required as there are no patients in this study.

Financial support and sponsorship

Nil.

Conflict of interest

There are is no conflict of interest.

Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation

The authors confirms that there was no use of Artificial Intelligence (AI)-Assisted Technology for assisting in the writing or editing of the manuscript and no images were manipulated using the AI.

References

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