Role of STAT6 rs3024974 (C/T) polymorphism in eliciting food sensitization among West Bengal population, India Arghya Laha1,3, Saibal Moitra2, Goutam Kumar Saha3, Sanjoy Podder1* 1. Department of Zoology, University of Burdwan, Bardhaman-713104, West Bengal, India. 2. Allergy and Asthma Research Centre, Kolkata- 700029, West Bengal, India. 3. Department of Zoology, University of Calcutta, Kolkata- 700019, West Bengal, India. BACKGROUND
STAT6 rs3024974 (C/T) genotype and allele frequencies
STAT6 rs3024974 polymorphism
Occurrence
of allergies towards commonly available foods raised from 10% to 30% in last 4 decades in India (Laha et al. 2020). Like other diseases, food allergies also has a genetic background. Genome wide association studies (GWAS) have identified STAT6 as a potential candidate genes. But, information in this regard mainly from western and developed countries but from India – fragmentary.
A. Patients vs. Control
Position: Intron 18
Age & sex adjusted OR CC 77 65 1.62 [0.69 to 3.76] 1.60 2.21 CT 51 59 1.18 [0.50 to 2.80] 1.17 (p= 0.331) TT 11 15 1 1 C allele 205 189 1.96 1.32 [0.92 to 1.91] 1.32 (p= 0.161) T allele 73 89 1 1 B. According to age of onset Genotype/ Childhood Adult Chi square OR [95%CI] Allele onset onset (p value) CC 40 37 1.30 [0.36 to 4.61] 2.67 CT 19 32 0.71 [0.19 to 2.66] (p= 0.264) TT 5 6 1 C allele 99 106 1.26 1.42 [0.82 to 2.44] (p= 0.261) T allele 29 44 1
Ancestral/Polymorphic allele: C/T; Genotypes: CC, CT and TT
Genotype/ Allele
Role in STAT6 physiology: CC genotype associated with increased production of IgE. HCV infected Taiwanese Chinese (Lim et al. 2013)
Asthma (Duetsch et al. 2002; Godava et al. 2013)
Hepatocellular carcinoma (Liao et al. 2015)
Past associations Clinical Malaria in Ghanaian Children (Amoako-Sakyi et al. 2016)
Schistosomiasis among Nigerian school children (Adedokun et al. 2018)
Psoriasis in North-eastern China (Zhou et al. 2017)
No association reported with food allergy till date; although specific IgE level in patients serum is an important indicator of food sensitization!!!!
WORK PLAN No wheal or a wheal not larger in size than that produced at the negative control site. Wheal diameter ≥3mm as compared to positive control. + Mild: 3 - 5mm; Moderate: 5 - 7mm; Severe: >7mm
Patients
Control
Chi square (p value)
A. Childhood onset (<20 years)
OR [95%CI]
B. Adult Onset (>20 years)
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Skin Prick Test 198 bp
Serum with antibodies
115 bp 83 bp
Blood cells
Total IgE determination by Enzyme Immune Assay Specific IgE determination by Pharmacia ImmunoCap CONCLUSION
C/C C/T T/T
C C
C
T
T
T
PCR PRODUCT (198 bp)
• IgE switching in B cells • Production of IL4, IL13
Genotype confirmation by sequencing and band pattern
RESTRICTION DIGESTION PstI (5’-CTGCAG-3’)
Significant association of rs3024974 SNP of STAT6 gene with elevated food specific IgE; prevalence of polymorphic CC genotypes in West Bengal population. STAT6 rs3024974
Marker
Target specific therapeutics
Acknowledgements CSIR, Govt. of India (08/606(0004)/2017-EMR-I dt 14/11/2017) DST, Govt. of West Bengal (1170(Sanc.)/ST/P/S&T/1G-4/2016, dt. 02.03.16).