TY - JOUR
T1 - Genetic Analysis of TB Susceptibility Variants in Ghana Reveals Candidate Protective Loci in SORBS2 and SCL11A1 Genes
AU - Asante-Poku, Adwoa
AU - Morgan, Portia
AU - Osei-Wusu, Stephen
AU - Aboagye, Samuel Yaw
AU - Asare, Prince
AU - Otchere, Isaac Darko
AU - Adadey, Samuel Mawuli
AU - Mnika, Khuthala
AU - Esoh, Kevin
AU - Mawuta, Kenneth Hayibor
AU - Arthur, Nelly
AU - Forson, Audrey
AU - Mazandu, Gaston Kuzamunu
AU - Wonkam, Ambroise
AU - Yeboah-Manu, Dorothy
N1 - Publisher Copyright:
Copyright © 2022 Asante-Poku, Morgan, Osei-Wusu, Aboagye, Asare, Otchere, Adadey, Mnika, Esoh, Mawuta, Arthur, Forson, Mazandu, Wonkam and Yeboah-Manu.
PY - 2022/2/15
Y1 - 2022/2/15
N2 - Despite advancements made toward diagnostics, tuberculosis caused by Mycobacterium africanum (Maf) and Mycobacterium tuberculosis sensu stricto (Mtbss) remains a major public health issue. Human host factors are key players in tuberculosis (TB) outcomes and treatment. Research is required to probe the interplay between host and bacterial genomes. Here, we explored the association between selected human/host genomic variants and TB disease in Ghana. Paired host genotype datum and infecting bacterial isolate information were analyzed for associations using a multinomial logistic regression. Mycobacterium tuberculosis complex (MTBC) isolates were obtained from 191 TB patients and genotyped into different phylogenetic lineages by standard methods. Two hundred and thirty-five (235) nondisease participants were used as healthy controls. A selection of 29 SNPs from TB disease-associated genes with high frequency among African populations was assayed using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Using 26 high-quality SNPs across 326 case-control samples in an association analysis, we found a protective variant, rs955263, in the SORBS2 gene against both Maf and Mtb infections (PBH = 0.05; OR = 0.33; 95% CI = 0.32–0.34). A relatively uncommon variant, rs17235409 in the SLC11A1 gene was observed with an even stronger protective effect against Mtb infection (MAF = 0.06; PBH = 0.04; OR = 0.05; 95% CI = 0.04–0.05). These findings suggest SLC11A1 and SORBS2 as a potential protective gene of substantial interest for TB, which is an important pathogen in West Africa, and highlight the need for in-depth host-pathogen studies in West Africa.
AB - Despite advancements made toward diagnostics, tuberculosis caused by Mycobacterium africanum (Maf) and Mycobacterium tuberculosis sensu stricto (Mtbss) remains a major public health issue. Human host factors are key players in tuberculosis (TB) outcomes and treatment. Research is required to probe the interplay between host and bacterial genomes. Here, we explored the association between selected human/host genomic variants and TB disease in Ghana. Paired host genotype datum and infecting bacterial isolate information were analyzed for associations using a multinomial logistic regression. Mycobacterium tuberculosis complex (MTBC) isolates were obtained from 191 TB patients and genotyped into different phylogenetic lineages by standard methods. Two hundred and thirty-five (235) nondisease participants were used as healthy controls. A selection of 29 SNPs from TB disease-associated genes with high frequency among African populations was assayed using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Using 26 high-quality SNPs across 326 case-control samples in an association analysis, we found a protective variant, rs955263, in the SORBS2 gene against both Maf and Mtb infections (PBH = 0.05; OR = 0.33; 95% CI = 0.32–0.34). A relatively uncommon variant, rs17235409 in the SLC11A1 gene was observed with an even stronger protective effect against Mtb infection (MAF = 0.06; PBH = 0.04; OR = 0.05; 95% CI = 0.04–0.05). These findings suggest SLC11A1 and SORBS2 as a potential protective gene of substantial interest for TB, which is an important pathogen in West Africa, and highlight the need for in-depth host-pathogen studies in West Africa.
KW - Ghana
KW - SLC11A1
KW - Sorbs2
KW - genomics
KW - tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85125662389&partnerID=8YFLogxK
U2 - 10.3389/fgene.2021.729737
DO - 10.3389/fgene.2021.729737
M3 - Article
AN - SCOPUS:85125662389
SN - 1664-8021
VL - 12
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 729737
ER -