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Current Pharmacogenomics and Personalized Medicine

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ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

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Research Article

Single Nucleotide Polymorphisms of MTHFR (rs1051266) and SLC19A1 (rs1801133) Associated to Genomic Ancestry in Cuban Healthy Population

Author(s): Goitybell Martínez*, Yaima Zuñiga, Jonas Bybjerg, Ole Mors and Beatriz Marcheco

Volume 20, Issue 2, 2023

Published on: 10 October, 2023

Page: [106 - 115] Pages: 10

DOI: 10.2174/1875692120666230816152420

Price: $65

Abstract

Background: Several single nucleotide polymorphisms on methotrexate pathway have been implicated with hyperhomocysteinemia, susceptibility to autoimmune diseases and the therapy effectiveness of methotrexate.

Objective: The present study estimates the ethnogeographic prevalence of rs1801133 (c.665C>T) in methylenetetrahydrofolate reductase and rs1051266 (c.80A>G) in solute carrier family 19 member 1, according to genomic ancestry analysis in Cuba healthy population.

Methods: Genomic data was collected from a dense genome-wide genotyping array analysis of a large sample of individuals from all provinces of Cuba, with a final sample of 946 individuals for rs1801133 and 948 individuals for rs1051266.

Results: For rs1801133, T allele and TT genotype were more prevalent in Mayabeque, the province with the highest European (p<0.0001) and the lowest African ancestry proportion (p<0.0001). Whereas, T allele and TT genotype frequency were low in Guantánamo (23.7% and 1.8%), the province with the highest African ancestry proportion (p<0.0001) and the lowest European ancestry proportion (p<0.0001). For rs1051266, the higher frequency of G allele was observed in Villa Clara, Las Tunas, Holguín and Granma and this group was associated with AG and GG genotypes (p=0.0045). This seems to be related to high Native American ancestry proportion in Las Tunas (p<0.0001), Holguín (p<0.0001) and Granma (p<0.0001); with the low African ancestry proportion in Villa Clara (p<0.0001) and with a Native American ancestry-enriched pattern observed for these provinces (p=0.0005).

Conclusion: These results provide evidence that ancestry contribution impacts in the ethnogeographic prevalence of rs1801133 (c.665C>T) and rs1051266 (c.80A>G) polymorphisms in healthy Cuban individuals.

Keywords: Single nucleotide polymorphism, methotrexate, methylenetetrahydrofolate reductase, solute carrier family 19 member 1, ancestry, methotrexate.

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Graphical Abstract

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