A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated with Plasmodium falciparum Infection in Children Residing in Burkina Faso
Abstract
:1. Introduction
2. Results
2.1. Prioritization and Annotation of Putative Regulatory SNPs in the Non-Coding FCGR Gene Cluster
2.2. Analysis of Allelic and Genotypic Frequencies of Non-Coding Regulatory and Coding FCGR2A/2B Variants in Burkina Faso Population
2.3. The Non-Coding rs1771575 Regulatory Variant Is Associated with Plasmodium falciparum Infection
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Phenotyping
4.3. Bioinformatic Identification of Non-Coding Variants
4.4. Genotyping of FCGR Variants
4.5. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Functional Regulatory Annotation | ||||||
---|---|---|---|---|---|---|
SNP | Position a | Annotation b | % Genotyped | ATAC-Seq c | ReMap c | Encode Regulatory Element |
rs1771575 (T > C) | 161647707 | intergenic | 100.0 | DC, Mo, NK, B | Mo, Ma, N, B | E1391464 |
rs2099684 (A > G) | 161530340 | intergenic | 96.5 | DC, NK | Mo, B | E1391397 |
rs1801274 (G > A) | 161509955 | FCGR2A exon, missense H-R | 97.4 | - | - | - |
rs1050501 (T > C) | 161674008 | FCGR2B exon, missense I-N | 97.5 | - | - | - |
eQTLs from ImmuNexUT Database | eQTLs from EBI Catalog | |||||
---|---|---|---|---|---|---|
Target Gene | Cell Type | p Value a | Target Gene | Cell Type | p Value b | |
rs1771575 | FCGR2B | Neutrophils | 3.10 × 10−38 | FCGR2B | Neutrophils | 1.15 × 10−10 |
FCGR3A | Neutrophils | 6.02 × 10−26 | FCGR2B | Monocyte, naive | 9.77 × 10−7 | |
FCGR2C | Dendritic cells | 2.77 × 10−17 | - | - | - | |
FCGR3B | NK cells | 1.16 × 10−5 | - | - | - | |
FCGR2A | Dendritic cells | 2.87 × 10−4 | - | - | - | |
rs2099684 | FCGR3B | NK cells | 8.54 × 10−78 | FCGR3B | Monocyte, naive | 6.31 × 10−23 |
FCGR2C | NK cells | 2.63 × 10−17 | FCGR3B | Monocyte, LPS | 1.35 × 10−18 | |
FCGR2A | Neutrophils | 6.68 × 10−15 | FCGR3B | Monocyte, IAV | 3.24 × 10−18 | |
FCGR2B | Neutrophils | 1.227 × 10−5 | FCGR3B | Monocyte | 3.55 × 10−17 | |
- | - | - | FCGR3B | NK-cell, naive | 4.68 × 10−16 | |
- | - | - | FCGR3B | Macrophage, Salmonella | 1.78 × 10−13 | |
- | - | - | FCGR3B | Macrophage, naive | 5.62 × 10−13 | |
- | - | - | FCGR3B | Macrophage, Listeria | 6.17 × 10−13 | |
- | - | - | FCGR3B | CD16 Monocyte, naive | 1.07 × 10−11 |
Parents | Children | |
---|---|---|
(N = 98) | (N = 136) | |
Gender | ||
N | 98 | 136 |
Female | 65 | 71 |
Male | 33 | 65 |
Ethnic group: Bobo a N | 98 | 136 |
Age | ||
N | 98 | 136 |
Median | 39 | 8 |
(25–75th percentile) | (31–45) | (6–12) |
Number of parasitaemia measurements per subject | ||
N | 98 | 136 |
Median | 18 | 20 |
(25th and 75th percentile) | (13–23) | (14–24) |
Phenotypes related to infection levels (PrevPfI) | ||
N | 98 | 136 |
Median | 0.14 | 0.57 |
(25th and 75th percentile) | (0.07–0.22) | (0.43–0.75) |
Explanatory Variable: PrevPfI a | Univariate Analysis | Linear Multiple Regression Adjusted to Age | Family Based Linear Mixed Model | ||
---|---|---|---|---|---|
p | b Coefficient (IC) | p | b Coefficient (IC) | p | |
b Recessive Model | |||||
Children age | <0.001 * | −0.0225 [−0.0276; −0.0175] | <0.001 * | −0.023 (−0.028; −0.018) | <0.001 * |
rs1771575-CC vs. CT/TT | 0.012 * | 0.0883 [0.0177; 0.159] | 0.015 * | 0.087 (0.017; 0.158) | 0.016 * |
c Additive Model | |||||
Children age | <0.001 * | −0.0227 [−0.0277; −0.0177] | <0.001 * | −0.023 (−0.028; −0.018) | <0.001 * |
rs1771575- CC vs. -CT vs. -TT | 0.0252 * | −0.0525 [−0.0941; −0.0108] | 0.014 * | −0.052 (−0.094; −0.010) | 0.016 * |
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Cretin, J.; Adjemout, M.; Dieppois, C.; Gallardo, F.; Torres, M.; Merard, Z.; Sawadogo, S.A.; Picard, C.; Rihet, P.; Paul, P. A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated with Plasmodium falciparum Infection in Children Residing in Burkina Faso. Int. J. Mol. Sci. 2023, 24, 15711. https://doi.org/10.3390/ijms242115711
Cretin J, Adjemout M, Dieppois C, Gallardo F, Torres M, Merard Z, Sawadogo SA, Picard C, Rihet P, Paul P. A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated with Plasmodium falciparum Infection in Children Residing in Burkina Faso. International Journal of Molecular Sciences. 2023; 24(21):15711. https://doi.org/10.3390/ijms242115711
Chicago/Turabian StyleCretin, Jules, Mathieu Adjemout, Christelle Dieppois, Frederic Gallardo, Magali Torres, Zachary Merard, Serge Aimé Sawadogo, Christophe Picard, Pascal Rihet, and Pascale Paul. 2023. "A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated with Plasmodium falciparum Infection in Children Residing in Burkina Faso" International Journal of Molecular Sciences 24, no. 21: 15711. https://doi.org/10.3390/ijms242115711