Deletion of the APOBEC3B gene strongly impacts susceptibility to falciparum malaria |
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Authors: | Pankaj JhaSwapnil Sinha Kanika KanchanTabish Qidwai Ankita NarangPrashant Kumar Singh Sudhanshu S. PatiSanjib Mohanty Saroj K. MishraSurya K. Sharma Shally AwasthiVimala Venkatesh Sanjeev JainAnalabha Basu Shuhua Xu Mitali Mukerji Saman Habib |
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Affiliation: | a Genomics and Molecular Medicine, Institute of Genomics and Integrative Biology, CSIR, Delhi, India b Division of Molecular and Structural Biology, Central Drug Research Institute, CSIR, Lucknow, India c Ispat General Hospital, Rourkela, India d National Institute of Malaria Research Field Station, Rourkela, India e Chhatrapati Sahuji Maharaj Medical University (CSMMU), Lucknow, India f National Institute of Mental Health and Neuro Sciences, Bangalore, India g National Institute of BioMedical Genomics, Kalyani, Kolkata, India h Chinese Academy of Sciences and Max Planck Society (CAS-MPG), Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China |
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Abstract: | APOBEC3B, a gene involved in innate response, exhibits insertion-deletion polymorphism across world populations. We observed the insertion allele to be nearly fixed in malaria endemic regions of sub-Saharan Africa as well as populations with high malaria incidence in the past. This prompted us to investigate the possible association of the polymorphism with falciparum malaria. We studied the distribution of APOBEC3B, in 25 diverse Indian populations comprising of 500 samples and 176 severe or non-severe Plasmodium falciparum patients and 174 ethnically-matched uninfected individuals from a P. falciparum endemic and a non-endemic region of India. The deletion frequencies ranged from 0% to 43% in the Indian populations. The frequency of the insertion allele strikingly correlated with the endemicity map of P. falciparum malaria in India. A strong association of the deletion allele with susceptibility to falciparum malaria in the endemic region (non-severe vs. control, Odds ratio = 4.96, P value = 9.5E−06; severe vs. control, OR = 4.36, P value = 5.76E−05) was observed. Although the frequency of deletion allele was higher in the non-endemic region, there was a significant association of the homozygous deletion genotype with malaria (OR = 3.17, 95% CI = 1.10-10.32, P value = 0.0177). Our study also presents a case for malaria as a positive selection force for the APOBEC3B insertion and suggests a major role for this gene in innate immunity against malaria. |
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Keywords: | APOBEC3B Plasmodium falciparum Malaria endemicity Innate response Structural variation |
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