title: Deletion of the APOBEC3B gene strongly impacts susceptibility to falciparum malaria.
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.
authors: Genomics and Molecular Medicine, Institute of Genomics and Integrative Biology, CSIR, Delhi, India.
authors: Pankaj
authors: P
authors: Jha
authors: Swapnil
authors: S
authors: Sinha
authors: Kanika
authors: K
authors: Kanchan
authors: Tabish
authors: T
authors: Qidwai
authors: Ankita
authors: A
authors: Narang
authors: Prashant Kumar
authors: PK
authors: Singh
authors: Sudhanshu S
authors: SS
authors: Pati
authors: Sanjib
authors: S
authors: Mohanty
authors: Saroj K
authors: SK
authors: Mishra
authors: Surya K
authors: SK
authors: Sharma
authors: Shally
authors: S
authors: Awasthi
authors: Vimala
authors: V
authors: Venkatesh
authors: Sanjeev
authors: S
authors: Jain
authors: Analabha
authors: A
authors: Basu
authors: Shuhua
authors: S
authors: Xu
authors: Mitali
authors: M
authors: Mukerji
authors: Saman
authors: S
authors: Habib
mesh_terms: D000483:Alleles; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D019353:Endemic Diseases / Q000517:prevention & control*; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007194:India / Q000453:epidemiology; D017780:Malaria Vaccines / Q000235:genetics; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000235:genetics* / Q000517:prevention & control; D015778:Minor Histocompatibility Antigens; D016017:Odds Ratio; D010963:Plasmodium falciparum / Q000472:pathogenicity; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
chemical_list: D017780:Malaria Vaccines; D015778:Minor Histocompatibility Antigens; C495794:APOBEC3B protein, human; D003564:Cytidine Deaminase