Genetic Variants Linked to Malaria Severity in India
Author Information
Author(s): Sinha Swapnil, Mishra Shrawan K, Sharma Shweta, Patibandla Phani K, Mallick Prashant K, Sharma Surya K, Mohanty Sanjib, Pati Sudhanshu S, Mishra Saroj K, Ramteke Bheshaj K, Bhatt RM, Joshi Hema, Dash Aditya P, Ahuja Ramesh C, Awasthi Shally, Indian Genome Variation Consortium, Venkatesh Vimala, Habib Saman
Primary Institution: Central Drug Research Institute, Lucknow, India
Hypothesis
The study aims to examine the contribution of genetic variants in the TNF and FCGR2A genes in determining severity/resistance to P. falciparum malaria in Indian subjects.
Conclusion
Specific TNF and FCGR2A SNPs are associated with cytokine levels and disease severity/resistance in malaria patients from different regions of India.
Supporting Evidence
- Five TNF enhancer SNPs and the FCGR2A R131H SNP were analyzed for association with malaria severity.
- Significantly higher TNF levels were observed in patients with severe malaria.
- Minor alleles of -1031 and -863 SNPs were associated with increased susceptibility to severe malaria.
- The high-affinity IgG2 binding FcγRIIa AA genotype was significantly associated with protection from disease manifestation.
- Association of specific TNF and FCGR2A SNPs with cytokine levels was indicated in patients from areas with differential disease endemicity.
Takeaway
Scientists studied genes in Indian people to see if they affect how sick they get from malaria, and found some genes that can make people more or less sick.
Methodology
The study involved genotyping genetic variants in 1871 individuals from 55 populations, using DNA sequencing and ELISA to measure plasma TNF levels.
Potential Biases
Potential bias due to population stratification and the selection of ethnically-matched controls.
Limitations
The study may not account for all genetic factors influencing malaria severity due to the complexity of genetic interactions.
Participant Demographics
Participants included individuals from diverse ethnic backgrounds across India, with samples from both malaria-endemic and non-endemic regions.
Statistical Information
P-Value
0.028 for -1031C allele association with disease severity
Confidence Interval
95% CI = 1.03–3.4 for -1031C allele
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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