Ovalocytosis without band 3 gene 27-bp deletion and malaria infection

Abstract

Genetic adaptation to malaria is a longstanding research topic in anthropology and human genetics. Southeast Asian ovalocytosis (SAO) has been documented to have resistance to malaria; however, the implications of existing data are controversial. In particular, SAO resistance to malaria is unlcear in terms of the types of SAO, with/without the 27-base pair deletion in the band 3 gene (B3∆27). To shed light on the relationships between SAO and malaria, we surveyed Plasmodium infection, erythrocyte morphology, and the presence of the B3∆27 among the residents of a selected area in East Kalimantan, Indonesia where malaria is endemic. We screened peripheral blood smears (n = 128) for Plasmodium infection and erythrocyte morphology under a microscope, and then DNA was extracted from the smears to be used as a template for a polymerase chain reaction to detect the B3∆27. The prevalence of infection with Plasmodium including Plasmodium vivax and Plasmodium falciparum was approximately 30%. Among a total of 128 subjects, 9.4% and 18.0% showed moderate (ovalocytic cells: 30-49%) and severe (ovalocytic cells: 50-100%) ovalocytosis, respectively. A total of three B3∆27 carriers were identified. The data set was statistically analyzed and we observed that (1) higher ovalocytic rate resulted in lower malaria infection and (2) the B3∆27 did not prevent malaria infection. These results suggest that resistance of SAO to malaria is due to SAO without the B3∆27.

Malaria prevalence in Nias District, North Sumatra Province, Indonesia

“…The higher frequency of SAO in the population of malaria endemic area of Southeast Asia and Melanesia supports the hypothesis that this genetic defect provides relative resistance to malaria. Subsequent studies reported that erythrocytes from SAO subjects are not resistant to invasion by P. falciparum but that the condition is associated with protection against severe malaria in children [ 16 , 17 ]. The mechanism(s) by which SAO confers protection to severe malaria remains unclear but some evidence indicates that it may be associated with reduced cytoadherence [ 13 , 17 ].…”

“…Subsequent studies reported that erythrocytes from SAO subjects are not resistant to invasion by P. falciparum but that the condition is associated with protection against severe malaria in children [ 16 , 17 ]. The mechanism(s) by which SAO confers protection to severe malaria remains unclear but some evidence indicates that it may be associated with reduced cytoadherence [ 13 , 17 ]. In this regard, it is of particular interest to explore further whether the frequency of SAO, at least among the ethnic population of Indonesia, is associated with malaria endemicity.…”

Association between ovalocytosis and Plasmodium infection: a systematic review and meta-analysis

“…The included studies were published between 1977 and 2015, with the majority (43.8%) published between 2000 and 2010 16 , 17 , 28 , 31 , 32 , 35 , 37 . Study designs included cross-sectional studies (50.0%) 16 , 17 , 28 , 30 , 31 , 34 , 36 , 37 , case–control studies (18.8%) 26 , 27 , 29 , cohort studies (25.0%) 32 , 33 , 35 , 38 and both cohort and case–control studies (6.3%) 15 .…”

“…The included studies were published between 1977 and 2015, with the majority (43.8%) published between 2000 and 2010 16 , 17 , 28 , 31 , 32 , 35 , 37 . Study designs included cross-sectional studies (50.0%) 16 , 17 , 28 , 30 , 31 , 34 , 36 , 37 , case–control studies (18.8%) 26 , 27 , 29 , cohort studies (25.0%) 32 , 33 , 35 , 38 and both cohort and case–control studies (6.3%) 15 . Most studies were conducted in Papua New Guinea (68.8%) 15 , 16 , 26 , 28 , 29 , 32 – 36 , 38 , with the remainder in Indonesia (18.8%) 17 , 31 , 37 , Malaysia (6.3%) 30 and Thailand (6.3%) 27 .…”

The evolutionary origins of Southeast Asian Ovalocytosis

“…Individuals with SAO are characterized as having oval-shaped red blood cells with increased membrane rigidity and decreased anion transport, but no clinical symptoms beyond sporadic associations with anemia in both adults and neonates (Amato and Booth, 1977;Coetzer et al, 1996;Laosombat et al, 2005;Laosombat et al, 2010;O'Donnell et al, 1998;Reardon et al, 1993;Schofield et al, 1992). The deletion mutation that causes SAO removes 9 amino acids from within the 11 th exon of SLC4A1 and distinguishes SAO from other forms of ovalocytosis in Southeast Asia (Kimura et al, 2006;Patel et al, 2001).…”