Helicobacter pylori Genotyping from American Indigenous Groups Shows Novel Amerindian vacA and cagA Alleles and Asian, African and European Admixture

Abstract

It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America.

Polymorphism in the Helicobacter pylori CagA and VacA toxins and disease

“…144,148,[151][152][153][154]160 These studies show that most cagA positive H. pylori strains are associated with the vacA s1 and/ or m1 genotypes. 42,99,144,[150][151][152][153][154][155][161][162][163][164] Together these studies support the notion that individuals who carry cagA positive, vacA s1/m1 H. pylori isolates may be candidates for eradication therapy as a means to prevent severe disease (duodenal ulcers, peptic ulcer of Africa. As such, H. pylori has evolved mechanisms to persist within the harsh human gastric environment and may even serve to protect humans from diseases such as asthma, allergy, and esophageal cancer.…”

“…This variation has been used as a means to classify the EPIYA containing regions into motifs termed EPIYA-A, -B, -C, and -D. Furthermore, since geographic variability exists in grouping of these motifs, this has been used to classify CagA as either Western (contains EPIYA-A, -B, and -C, where the C motif may be duplicated multiple times) or East Asian (contains EPIYA-A, -B, and -D). 70,76,93,98 Recently the sequence and EPIYA motifs of two additional CagA motifs, J-Western and Amerindian, have also been characterized 10,[20][21][22]24,25,99 and compared with the Western and East Asian CagA EPIYA motifs (Fig. 2).…”

Coevolución genética Homo sapiens-Helicobacter pylori y sus implicaciones en el desarrollo del cáncer gástrico: una revisión sistemática

“…La variación genética en H. pylori tiene más poder discriminatorio en la determinación de las antiguas migraciones en la región de Ladakh del norte de la India y en el Pacífico (expansión austronesia), que los martante asociado con gastritis, que induce una respuesta inflamatoria, genera lesiones secuenciales preneoplásicas en la mucosa gástrica asociadas con el desarrollo de úlcera gastroduodenal, gastritis atrófica, displasia, CG y linfoma MALT (7,11,12,14,37). La colonización por H. pylori podría conferir protección contra la tuberculosis a través de la inducción de interferones antagónicos para el agente causal, Mycobacterium tuberculosis (39).…”

“…La bacteria Helicobacter pylori coevoluciona con el hombre desde su origen y es muy común en el microbioma intestinal -infecta a más del 50% de la población mundial y contribuye en un ~20% al desarrollo de enfermedades gás-tricas y CG (4,7,(12)(13)(14). Desde 1994, es considerada por la Agencia Internacional para la Investigación en Cáncer (IARC) como un carcinógeno tipo I, por ser la principal causa de cáncer relacionada con la infección en hombres y la segunda en mujeres después del cáncer de cuello uterino (1,8).…”

“…Dado que la filogenia étnico-geográfica de este pató-geno se define con cepas específicas para grandes áreas continentales y patrones geográficos de diversidad genética, paralelos a los de la diversidad humana (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), algunos estudios sugieren que las interacciones entre el genoma del huésped-patógeno, la disrupción en el proceso de coevolución por infección con cepas de origen ancestral distinto al del huésped, la transferencia horizontal de segmentos de genes que no han coevolucionado con sus anfitriones y la selección positiva de cepas introducidas podrían generar una alteración de la selección para virulencia y perturbar el proceso de coevolución, lo que explicaría las altas tasas de incidencia de CG en poblaciones humanas con alta diversidad genética como la colombiana, que posee una mezcla genética compleja de diferentes proporciones -amerindia, europea y africana-, debida a un proceso reciente de mezcla intercontinental (17).…”