The Lewis Histo-Blood Group System: Molecular Analysis of the 59T>G, 508G>A, and 1067T>A Polymorphisms in an Amazonian Population

Abstract

BackgroundThe Lewis (FUT3) gene is responsible for the expression of the Lea and Leb blood group antigens. The individuals, who not synthesize these antigens have the phenotype Lewis negative, due to the presence of some single nucleotide polymorphisms (SNPs), such as 59T>G, 508G>A and 1067T>A, whose distribution is different in various ethnic groups. Our aim was to verify the frequencies of these SNPs in an admixed population of Belém-Pará-Brazil.Materials and MethodsPolymerase chain reaction/restriction enzyme method were used to detect these SNPs in the FUT3 gene, whereas Lewis phenotypes were defined by the direct hemagglutination and in saliva by Dot-Elisa assay in a random sample of 150 individuals from admixed population of Belém in the northeast Brazilian Amazon region.ResultsThe frequency of these SNPs was detected as 47.6% (59T>G), 17.3% (508G>A) and 5.3% (1067T>A).The discrepancies between blood and salivary Lewis phenotypes are related to the relatively high frequencies of 59T>G and the null allele 508G>A. Whereas 38.6% of the individuals were Lewis negative based on blood, only 17.24% also tested negative when their saliva were analyzed.ConclusionWe have found a marked consistency between the phenotypes and genotypes of the Lewis blood group system. Furthermore, our obtained FST values reveal distinct frequencies of the FUT3 SNPs between the present sample and its representative ancestral populations. These observations will help to evaluate the Lewis antigens impact as susceptibility markers, in genetic association studies to certain diseases.

Distribution of Lewis and Secretor polymorphisms and corresponding CA19‐9 antigen expression in a Chinese population

“…Distribution of the FUT3 genotype is approximatively consistent with reported data in Chinese and other Asian populations. Nevertheless, no Asian population study has confirmed the existence of le 508 previously, which is at a frequency of 0.16% in the present study and 0.70% in an Amazonian population . le 59,508 is abundantly distributed in most populations with a frequency from 14% to 31%, but rarely found in Caucasians (1.0% and 1.5%).…”

“…Both FUT3 and FUT2 genes have no intron in the open reading frame and fewer reactions are capable of amplification of the complete mutation region. Three pairs of PCR primers respectively specific for the FUT3 and FUT2 gene segments are shown in Table S1, and sequence design partly referred to those previously reported . For each segment amplification, 20 ng of genomic DNA was combined with the primers (7.5 μ m for forward and reverse) in a PCR system of final volume 25 μL.…”

“…The fucosyltransferase diverts a fucose to either the type 1 precursor or the H type 1, to form Le a or Le b , respectively. Mutations in the FUT3 gene may result in the Lewis‐null phenotype (le) . SNPs rs28362459 (T59G), rs812936 (T202C), rs778986 (C314T), rs3745635 (G508A) and rs3894326 (T1067G) of the FUT3 gene are the most common polymorphic loci in Asians .…”

“…However, Lewis‐positive individuals (the Le / Le and Le / le genotypes) are divided into three Lewis‐secretor phenotypes according to distinct Secretor genotypes as follows: (a) Le (a−b+) secretors with the Se / Se or Se / se genotype; (b) Le (a+b−) non‐secretors with the se / se genotype; and (c) Le (a+b+) partial secretors having homozygosity for the weak Secretor allele . Nucleotide substitutions inactivating the FUT2 / 3 genes have been found within various populations, and the phenotypes have been determined by the ethnic group‐specific genotypes . Both genotypes of Lewis and Secretor are crucial for an individual's phenotype formation, and the serum CA19‐9 value will directly reflect the differences among individuals.…”

Blood Groups in Infection and Host Susceptibility

“…Many mutations show a distinct geographic or ethnic distribution. In Caucasians, alleles containing T202C (Trp68Arg) and C314T (Thr105Met) mutations are common (le 202,314 ), whereas le 59 , le 59,508 , and le 59,1067 are predominant in Japan, China, South Korea, northern India, Asia, and the Brazilian Amazon (2,29,(66)(67)(68)(69)(70)(71). In African and U.S. black populations, several additional SNPs have been identified, especially G13A (Gly5Ser), G484A (Asn162Asp), G667A (Gly223Arg), and A808G (Val270Met) (69,72,73).…”