Publications by authors named "Alexandra S Karunas"

4 Publications

  • Page 1 of 1

Association of Gasdermin B Gene GSDMB Polymorphisms with Risk of Allergic Diseases.

Biochem Genet 2021 May 8. Epub 2021 May 8.

Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.

The GSDMB gene encodes gasdermin B from the family of gasdermin domain-containing proteins involved in various cellular processes related to tumor development and progression, such as differentiation, cell cycle control and apoptosis. Previously, we conducted GWAS on asthma in the Volga-Ural region of Russia and found SNPs associated with asthma with genome-wide significance (rs9303277, rs8067378, rs2290400, rs7216389, rs4795405) and located in the chromosomal region 17q12-q21, which contains IKZF3 (IKAROS family zinc finger 3), ZPBP2 (zona pellucida binding protein-like), GSDMB (gasdermin B), ORMDL3 (orosomucoid 1-like 3) and LRRC3C (leucine-rich repeat-containing 3C) genes. In the present study, we investigated the association of SNPs of the GSDMB gene with the development of various allergic diseases and their combined manifestations in individuals of Russian, Tatar and Bashkir ethnic origin. Our results revealed that polymorphic variants rs7216389, rs2290400 and rs2305480 are associated with the development of allergic diseases as well as with asthma and asthma combined with allergic rhinitis. We did not reveal the association of rs7216389 and rs2290400 with the development of allergic rhinitis and atopic dermatitis in the groups of patients without asthma symptoms. This may reflect a more important role of these SNPs in the development of asthma.
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http://dx.doi.org/10.1007/s10528-021-10073-8DOI Listing
May 2021

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.

Nat Genet 2018 01 22;50(1):42-53. Epub 2017 Dec 22.

Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico.

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.
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http://dx.doi.org/10.1038/s41588-017-0014-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901974PMC
January 2018

The study of filaggrin gene mutations and copy number variation in atopic dermatitis patients from Volga-Ural region of Russia.

Gene 2016 Oct 28;591(1):85-89. Epub 2016 Jun 28.

Institute of Biochemistry and Genetics of Ufa Scientific Centre of Russian Academy of Sciences, Ufa 450054, Pr.Oktyabrya, 71, Russia; Bashkir State University, Ufa 450076, ul. Z.Validi, 32, Russia.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by age-specific localization, dryness, itch and hypersensitivity to allergens. In our study, we investigated FLG gene mutations and CNVs in AD patients and control subjects of different ethnic origin from Volga-Ural region. AD group included 303 patients (177 Russians, 126 Tatars). Control group consisted of 261 healthy individuals (152 Russians, 109 Tatars). The study revealed 66 FLG mutation carriers and demonstrated an association between c.2282del4 deletion and AD development in Russians and Tatars of Volga-Ural region of Russia. In the analysis of the FLG gene CNVs, the most common was 10-repeat allele in both Russian and Tatar patients and controls. We were unable to find any significant difference in CNV repeats count between AD patients and control individuals.
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http://dx.doi.org/10.1016/j.gene.2016.06.054DOI Listing
October 2016

Identification of a new locus at 16q12 associated with time to asthma onset.

J Allergy Clin Immunol 2016 10 6;138(4):1071-1080. Epub 2016 Apr 6.

Inserm, UMR-946, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France. Electronic address:

Background: Asthma is a heterogeneous disease in which age of onset plays an important role.

Objective: We sought to identify the genetic variants associated with time to asthma onset (TAO).

Methods: We conducted a large-scale meta-analysis of 9 genome-wide association studies of TAO (total of 5462 asthmatic patients with a broad range of age of asthma onset and 8424 control subjects of European ancestry) performed by using survival analysis techniques.

Results: We detected 5 regions associated with TAO at the genome-wide significant level (P < 5 × 10). We evidenced a new locus in the 16q12 region (near cylindromatosis turban tumor syndrome gene [CYLD]) and confirmed 4 asthma risk regions: 2q12 (IL-1 receptor-like 1 [IL1RL1]), 6p21 (HLA-DQA1), 9p24 (IL33), and 17q12-q21 (zona pellucida binding protein 2 [ZPBP2]-gasdermin A [GSDMA]). Conditional analyses identified 2 distinct signals at 9p24 (both upstream of IL33) and 17q12-q21 (near ZPBP2 and within GSDMA). Together, these 7 distinct loci explained 6.0% of the variance in TAO. In addition, we showed that genetic variants at 9p24 and 17q12-q21 were strongly associated with an earlier onset of childhood asthma (P ≤ .002), whereas the 16q12 single nucleotide polymorphism was associated with later asthma onset (P = .04). A high burden of disease risk alleles at these loci was associated with earlier age of asthma onset (4 vs 9-12 years, P = 10).

Conclusion: The new susceptibility region for TAO at 16q12 harbors variants that correlate with the expression of CYLD and nucleotide-binding oligomerization domain 2 (NOD2), 2 strong candidates for asthma. This study demonstrates that incorporating the variability of age of asthma onset in asthma modeling is a helpful approach in the search for disease susceptibility genes.
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http://dx.doi.org/10.1016/j.jaci.2016.03.018DOI Listing
October 2016