Evidence for malaria selection of a CR1 haplotype in Sardinia

Abstract

Complement receptor 1 (CR1) levels have been associated with malarial susceptibility and/or severity of the disease in different population groups, and CR1 is a receptor for Plasmodium falciparum. In this study, multiple CR1 single-nucleotide polymorphisms (SNPs) showed strong evidence of population differentiation between Sardinian and other European ethnic groups. Cross population algorithms comparing haplotype structure and differences in haplotype and allele frequency distribution provided additional support for natural selection of CR1 in Sardinia. The predominant Sardinian CR1 haplotype included SNPs that are associated with decreased CR1 levels in Europeans and other population groups. Previous studies have shown that the SNPs within the dominant Sardinian haplotype have a significantly higher frequency in a malaria endemic compared with non-endemic regions in India. Together with the historical evidence of the prevalence of malaria in Sardinia, these data support the role of malaria leading to positive selection of this CR1 haplotype in Sardinia.

Maternal longevity is associated with lower infant mortality

“…The AkeA researchers found that the gene pool in the Sardinians of the particularly remote mountainous region is relatively small (Carru et al 2003;Pes et al 2004). For example, the local people have small red blood cells, which is thought to protect them against malaria and help prevent blood clots (Kosoy et al 2011). Our results from Scenario C showed that infant mortality in Sardinia is lower in the mountainous areas where a large part of our centenarians mainly come from.…”

Association of Complement Receptor Type-1 (CD35) Gene Polymorphism with P. falciparum Malarial infection in Vindhyan region of Madhya Pradesh, India

“…In addition, African population, Another SNP of CR1, A4828G (R1601G), is highly prevalent in malaria endemic areas of Africa, but a study in Gambia showed that it was not associated with severe malaria [19]. However, the findings of a similar study of various European populations supported the role CR1 (CD35) polymorphism in malarial infection [20]. The work of A. Srivastava & B. Mittal for Indian population suggests that decreased expression of complement receptor 1 (CR1) on erythrocytes confirm reduced clearance of immune complexes, conferring inter individual variation for gallbladder cancer (GBC) susceptibility.…”

Population- and individual-specific regulatory variation in Sardinia

“…We also identified several regulatory variants for the CR1 gene whose product is involved in complement activation and immune complex formation during malaria infection 41,42 . CR1 has two eQTLs (chr1:g.207275799G>A and chr1:g.207667190G>C) and 9 sQTLs.…”