Prevalence of common hereditary risk factors for thrombophilia in Somalia and identification of a novel Gln544Arg mutation in coagulation factor V

Abstract

Thrombophilia, commonly manifested as venous thromboembolism (VTE), is a worldwide concern but little is known on its genetic epidemiology in many parts of the globe particularly in the developing countries. Here we employed TaqMan genotyping and pyrosequencing to evaluate the prevalence of known common nucleotide polymorphisms associated with thrombophilia in a Somali population in the Puntland region of Somalia. We also employed next generation sequencing (NGS) to investigate other genetic variants in a Somali patient with deep venous thrombosis (DVT). As expected, we found no existence of factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) in the Somali population. The G allele of ABO [261G/delG] polymorphism (rs8176719) was found at a frequency of 29%, similar to that observed in other African populations. We found the lowest so far reported frequency of MTHFR C677T (rs1801133) polymorphism in the Somali population (T allele frequency 1.5%). A novel and deleterious single nucleotide variation in exon 11 of coagulation factor V (c.1631A>G) causing Gln544Arg exchange in factor V was identified in a 29 years old Somali female with DVT. The same patient was heterozygous to VKORC1 Asp36Tyr polymorphism (rs61742245) that predisposes to warfarin resistance. In conclusion, this study shows that common hereditary factors for thromboembolism found in Caucasians are either less frequent or absent in the Somali population—similar to the situation in other Africans. NGS is possibly a better choice to detect genetic risk variants for thrombosis in this ethnic group.

Genome-wide analyses disclose the distinctive HLA architecture and the pharmacogenetic landscape of the Somali population

“…The proportion of Rh+ and Rh-were 88% and 12%, respectively. These results were consistent with the previously reported Somali phenotype blood group data 26 as well as with our previous O blood group genotype assessments for ethnic Somalis 27 . We also examined the distribution of Apolipoprotein E (ApoE) gene variants in the Somali population using the SNPs rs429358 and rs7412.…”

Prevalence of thrombophilia-associated genetic risk factors in blood donors of a regional hospital in southern Brazil

“…A study conducted in Somalia showed that these common genetic risk factors, most known for VTE, are absent or less frequent in this group, when compared to other ethnic populations. 35 Our population had very few individuals of Afro-descendant origin (3%), which could explain the higher prevalence of these variants. However, this study was limited by its sample size.…”

Cross-ethnic analysis of common gene variants in hemostasis show lopsided representation of global populations in genetic databases

“…One of these, rs61742245 (VKORC1 Asp36Tyr), was prevalent only in the SOM population. This variant is included in the 8% ‘C G C C G G A A’ haplotype in Table 1 , as mentioned above, and is associated with warfarin resistance in the Horn of Africa [ 19 – 21 ] and, to a lesser extent, in the Middle East [ 22 , 23 ]. The two genetically most distinct populations from Europe (YRI and EAS) had also the fewest number of drug response variants that reached the threshold of 1% AAF.…”