Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease
Abstract
:1. Introduction
2. The Role of CCR5 in Disease
2.1. Cardiovascular Diseases
2.2. Diseases of the Nervous System
2.3. Immune System Diseases
2.4. Infectious Diseases
2.4.1. Acquired Immunodeficiency Syndrome
2.4.2. West Nile Fever
2.4.3. Hepatitis B Infection
2.4.4. Hepatitis C Infection
2.4.5. Chagas Disease
2.4.6. Influenza A
2.5. Cancer
3. Conclusions
Funding
Conflicts of Interest
Abbreviations
CCR5 | C-C chemokine receptor 5 |
kDa | kilodalton |
CMI | Cell-mediated immunity |
MIP1-α | Macrophage inflammatory protein one alpha |
MIP1-β | Macrophage inflammatory protein one beta |
RANTES | Regulated upon activation, normal T-cell expressed and secreted |
CCL5 | C-C chemokine ligand 5 |
MCP-2 | Monocyte chemotactic protein two |
Th1 | T helper type 1 |
Th2 | T helper type 2 |
ATP | Adenosine triphosphate |
LDL | Low-density lipoprotein |
HDL | High-density lipoprotein |
∆32 | 32-base pair deletion |
bp | Base pairs |
WT | Wild type |
HIV-1 | Human immunodeficiency virus |
AIDS | Acquired immunodeficiency syndrome |
CCR5+ | CCR5-positive |
CRISPR | Clustered regularly interspaced short palindromic repeats |
DNA | Deoxyribonucleic acid |
UK | United Kingdom |
CVD | Cardiovascular disease |
MCP-1 | Monocyte chemoattractant protein-1 |
CAD | Coronary artery disease |
CRP | C-reactive protein |
ELISA | Enzyme-linked immunosorbent assay |
PCR | Polymerase chain reaction |
HDL-C | High-density lipoprotein cholesterol |
TG | Triglycerides |
LDL-C | Low-density lipoprotein cholesterol |
RFLP | Restriction fragment length polymorphism |
MI | Myocardial infarction |
ICAS | Ischemic carotid artery stenosis |
AD | Alzheimer’s disease |
PD | Parkinson’s disease |
ms | Multiple sclerosis |
RT-PCR | Reverse-transcription polymerase chain reaction |
LOAD | Late-onset Alzheimer’s disease |
mRNA | Messenger ribonucleic acid |
IgE | Immunoglobulin E |
T2DM | Type 2 diabetes mellitus |
HbA1c | Haemoglobin A1c |
T1DM | Type 1 diabetes mellitus |
RA | Rheumatoid arthritis |
RF | Rheumatoid factor |
JIA | Juvenile idiopathic arthritis |
SLE | Systemic lupus erythematosus |
LN | Lupus nephritis |
SDF-1 | Stromal cell-derived factor one |
WNV | West Nile virus |
WNF | West Nile fever |
HBV | Hepatitis B virus |
NK | Natural killer |
HCV | Hepatitis C virus |
CCR5- | CCR5-negative |
HPV | Human papillomavirus |
HPV+ | Human papillomavirus-positive |
AML | Acute myeloid leukaemia |
MS | Mass spectrometry |
AS | Atherosclerosis |
CHD | Coronary heart disease |
CM | Cardiomyopathy |
HT | Hypertension |
NS | Nervous system |
IS | Immune system |
ID | Infectious disease |
CD | Chagas disease |
BC | Breast cancer |
PanC | Pancreatic cancer |
CC | Cervical cancer |
GallC | Gallbladder cancer |
GasC | Gastric cancer |
PC | Prostate cancer |
CCL3 | C-C chemokine ligand 3 |
CCL4 | C-C chemokine ligand 4 |
NP | Non-protective |
PP | Partially protective |
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Reference | [61] | [62] | [63] | [64] | [65] | [66] | [67] | [68] | [69] | [70] | |
---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | CVD | CVD | CVD | CVD | CVD | CVD | CVD | CVD | CVD | CVD | |
Disease | AS | CHD | CAD | CAD | CAD | CAD | CAD | CM | CAD | CAD | |
Population | Mixed | Caucasian | Caucasian | Greek | German; Caucasian | Indian | Bruneck | German | Hungarian | Mixed | |
Model | Meta-analysis | Blood | Blood | Blood | Blood | Blood | Blood | Blood | Blood | Meta-analysis | |
CCR5∆32 frequency | Patients | ↑ Asian | ↑ | ||||||||
No difference | X Mixed | X | X | X | X | X | X | ||||
Controls | |||||||||||
CCR5 levels | Patients/test subject/sample | ||||||||||
No difference | |||||||||||
Controls | |||||||||||
Genotype | Homozygous CCR5∆32 | X Asian | X | X | X | X | X | ||||
Heterozygous CCR5∆32 | X Asian | X | X | X | X | X | X | ||||
Absent CCR5∆32 | X Px | X a | X a | X Px,a | |||||||
Homozygous WT | X | ||||||||||
Association/effect of CCR5∆32 | Protective | X a | X | X M | X a | ||||||
No association/effect | X S, Mixed | X b | X | X S | X b,S | X | |||||
Risk factor/non-protective | X S,Asian | X O | X S | ||||||||
Assay(s) used | PCR | X | X | X | X | X | X | X | X | ||
RFLP | X | X | |||||||||
Sequencing | |||||||||||
Immune-based | X | X | X | X | |||||||
Microscopy | |||||||||||
Spectroscopy | X | X | |||||||||
Flow Cytometry | |||||||||||
Chromatography | |||||||||||
MS | |||||||||||
Other | Meta-analysis | Meta-analysis | |||||||||
Parameters | Immune | X | X | X | |||||||
Metabolic | X | X | X | X | X | X |
Reference | [72] | [73] | [74] | [75] | [76] | [77] | [84] | [85] | [86] | [87] | |
---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | CVD | CVD | CVD | CVD | CVD | CVD | NS | NS | NS | NS | |
Disease | MI | MI | MI | ICAS | HT | HT | AD | AD | AD | AD | |
Population | Sicilian | Caucasian | Turkish | Italian | Caucasian | Caucasian | Spanish | Italian | Italian | Iranian | |
Model | Blood | Blood | Blood | Blood | Blood | Blood | Blood | Blood | Blood | Blood | |
CCR5∆32 frequency | Patients | ↑ >60 years | ↑ a,b | ↑ a,b | |||||||
No difference | X | X | X | X | X | X | |||||
Controls | ↑ | ↑ <55 years | |||||||||
CCR5 levels | Patients/test subject/sample | ||||||||||
No difference | |||||||||||
Controls | |||||||||||
Genotype | Homozygous CCR5∆32 | X | X | X | X | X | |||||
Heterozygous CCR5∆32 | X | X | X | X | X | X | |||||
Absent CCR5∆32 | X a | ||||||||||
Homozygous WT | |||||||||||
Association/ effect of CCR5∆32 | Protective | X | X <55 years | ||||||||
No association/effect | X | X | X | X P | X | X | |||||
Risk factor/non-protective | X >60 years | X a,b | X a,b | ||||||||
Assay(s) used | PCR | X | X | X | X | X | X | X | X | X | X |
RFLP | X | X | X | X | |||||||
Sequencing | |||||||||||
Immune-based | |||||||||||
Microscopy | |||||||||||
Spectroscopy | |||||||||||
Flow Cytometry | |||||||||||
Chromatography | |||||||||||
MS | |||||||||||
Other | |||||||||||
Parameters | Immune | ||||||||||
Metabolic | X |
Reference | [88] | [90] | [91] | [92] | [93] | [94] | [95] | [96] | [97] | [100] | [101] | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | NS | NS | NS | NS | NS | NS | NS | NS | NS | IS | IS | |
Disease | AD | PD | ms | ms | ms | ms | ms | ms | ms | Asthma | Asthma | |
Population | N/A | Spanish | Caucasian | Finland | Israeli | Dutch | Australian | Brazilian | Irish | Scottish | Scottish | |
Model | Mice | Blood | Tissue; Blood | Blood | Blood | Blood; Brain Tissue | Blood | Blood | Blood | Cells | Blood | |
CCR5∆32 frequency | Patients | ↑ a | ↑ | |||||||||
No difference | X | X | X | X | X | |||||||
Controls | ||||||||||||
CCR5 levels | Patients/test subject/sample | ↓ | ↓ | |||||||||
No difference | ||||||||||||
Controls | ||||||||||||
Genotype | Homozygous CCR5∆32 | X | X | X | ||||||||
Heterozygous CCR5∆32 | X | X | X | X | ||||||||
Absent CCR5∆32 | X a | X Px | XPx,a,CA | |||||||||
Homozygous WT | ||||||||||||
Association/ effect of CCR5∆32 | Protective | X | X P,C | X | X O,b | X | X CA | |||||
No association/effect | X S,C | X S | X S | X S,C | X S | X S,C | X S,C,P | |||||
Risk factor/non-protective | X C,M | X S,C | X O | |||||||||
Assay(s) used | PCR | X | X | X | X | X | X | X | X | X | X | X |
RFLP | X | |||||||||||
Sequencing | X | |||||||||||
Immune-based | X | |||||||||||
Microscopy | ||||||||||||
Spectroscopy | ||||||||||||
Flow Cytometry | X | |||||||||||
Chromatography | ||||||||||||
MS | ||||||||||||
Other | ||||||||||||
Parameters | Immune | X | ||||||||||
Metabolic |
Reference | [103] | [104] | [105] | [106] | [24] | [110] | [111] | [112] | [113] | [114] | [115] | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | IS | IS | IS | IS | IS | IS | IS | IS | IS | IS | IS | |
Disease | Asthma | Asthma | Asthma | T2DM | T2DM | T1DM | T1DM | T1DM | T1DM; T2DM | Asthma; T1DM | RA | |
Population | Mixed | Iranian | Polish | Dutch; Swedish | N/A | Italian | Hungarian | British | Estonian | Mixed | Brazilian | |
Model | Blood | Blood | Blood | Blood; Urine | Rats: Blood; Tissue | Blood | Blood | Blood | Blood | Meta-Analysis | Blood; Synovial fluid | |
CCR5∆32 frequency | Patients | |||||||||||
No difference | X | X | X | X | X | X | ||||||
Controls | ↑ b | |||||||||||
CCR5 levels | Patients/test subject/sample | ↓ | ↑ CCR5+cells | |||||||||
No difference | ||||||||||||
Controls | ||||||||||||
Genotype | Homozygous CCR5∆32 | X | X | X | ||||||||
Heterozygous CCR5∆32 | X | X | X | X | X | X Px | ||||||
Absent CCR5∆32 | XPx,a | Xa | ||||||||||
Homozygous WT | ||||||||||||
Association /effect of CCR5∆32 | Protective | X M | X C | X C,b | X T1DM | |||||||
No association/effect | X | X | X | X S | X | X | X S | X Asthma | X | |||
Risk factor/non-protective | X * | |||||||||||
Assay(s) used | PCR | X | X | X | X | X | X | X | X | X | X | |
RFLP | X | |||||||||||
Sequencing | X | |||||||||||
Immune-based | X | X | ||||||||||
Microscopy | ||||||||||||
Spectroscopy | ||||||||||||
Flow Cytometry | X | |||||||||||
Chromatography | X | |||||||||||
MS | ||||||||||||
Other | Meta-analysis | |||||||||||
Parameters | Immune | X | X | |||||||||
Metabolic | X |
Reference | [116] | [117] | [118] | [119] | [120] | [122] | [123] | [124] | [126] | [30] | |
---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | IS | IS | IS | IS | IS | IS | IS | IS | IS | ID | |
Disease | RA; JIA | RA | RA; SLE | RA | RA | SLE | SLE; LN | SLE | LN | AIDS | |
Population | Norwegian | Danish | Caucasian | New Zealand | German | Portuguese | Brazilian | Brazilian | Mixed | Mixed | |
Model | Blood | Blood | Blood | Blood | Blood | Blood | Blood | Blood | Meta-analysis | Meta-analysis | |
CCR5∆32 frequency | Patients | ↓ b | ↑ * | ↓ b | ↓ European; ↑ African | ↑ | ↑ a,b,EU | ||||
No difference | X | X | X SLE | X | |||||||
Controls | |||||||||||
CCR5 levels | Patients/test subject/sample | ||||||||||
No difference | |||||||||||
Controls | |||||||||||
Genotype | Homozygous CCR5∆32 | X | X C | X | X | X | X | ||||
Heterozygous CCR5∆32 | X | X C | X | X | X | X | X | X | X | ||
Absent CCR5∆32 | X Px (RA),a | X Px,a | X Px,a | X Px,a (European) | |||||||
Homozygous WT | X | ||||||||||
Association /effect of CCR5∆32 | Protective | X C | X RA,a | Xa | X S,C | X | X SLE-European | X S,P | |||
No association/effect | X | X SLE | X C | X C | X S,Caucasian,Asian | ||||||
Risk factor/non-protective | X LN African | X S,O | X African | ||||||||
Assay(s) used | PCR | X | X | X | X | X | X | X | X | ||
RFLP | |||||||||||
Sequencing | |||||||||||
Immune-based | X | X | |||||||||
Microscopy | |||||||||||
Spectroscopy | |||||||||||
Flow Cytometry | |||||||||||
Chromatography | |||||||||||
MS | |||||||||||
Other | X | Meta-analysis | Meta-analysis | ||||||||
Parameters | Immune | X | |||||||||
Metabolic |
Reference | [31] | [33] | [37] | [128] | [129] | [130] | [131] | [132] | [133] | [134] | |
---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | ID | ID | ID | ID | ID | ID | ID | ID | ID | ID | |
Disease | AIDS | AIDS | AIDS | AIDS | AIDS | AIDS | AIDS | AIDS | AIDS | AIDS | |
Population | Caucasian | Black South African | Caucasian | European descent | Human | Italian | European descent | American | Caucasian | N/A | |
Model | Cells | Blood | Blood | Cells | Cells | Blood; cells | Blood | Blood | Blood | Blood | |
CCR5∆32 frequency | Patients | ↓ b | |||||||||
No difference | X | ||||||||||
Controls | |||||||||||
CCR5 levels | Patients/test subject/sample | ↓ | X NE | ||||||||
No difference | |||||||||||
Controls | |||||||||||
Genotype | Homozygous CCR5∆32 | X | X | X | X | X | X | X | X | X | |
Heterozygous CCR5∆32 | X | X | |||||||||
Absent CCR5∆32 | X Px,a | ||||||||||
Homozygous WT | |||||||||||
Association /effect of CCR5∆32 | Protective | X | X | X S,P | X | X | |||||
No association/effect | |||||||||||
Risk factor/non-protective | X | X | X | X | X | ||||||
Assay(s) used | PCR | X | X | X | X | X | X | X | X | X | X |
RFLP | |||||||||||
Sequencing | X | X | X | X | X | X | |||||
Immune-based | X | X | X | X | |||||||
Microscopy | X | ||||||||||
Spectroscopy | X | ||||||||||
Flow Cytometry | X | X | |||||||||
Chromatography | |||||||||||
MS | |||||||||||
Other | |||||||||||
Parameters | Immune | X | |||||||||
Metabolic |
Reference | [135] | [136] | [137] | [138] | [139] | [144] | [145] | [146] | [148] | [149] | [153] | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | ID | ID | ID | ID | ID | ID | ID | ID | ID | ID | ID | |
Disease | AIDS | AIDS | WNF | WNF | WNF | HBV | HBV | HBV | HBV | HBV/HIV-1 | HCV | |
Population | Caucasian | Caucasian | N/A | Caucasians | American | N/A | Iranian | Iranian | Caucasian | Brazilian | Mixed | |
Model | Blood | Blood | Mice | Blood; CSF | Meta-analysis | Blood; CD4+ cells | Blood; NK cells | Blood; CD8+ cells | Blood | Blood | Blood | |
CCR5∆32 frequency | Patients | ↑ Recovery | ||||||||||
No difference | X | |||||||||||
Controls | ||||||||||||
CCR5 levels | Patients/test subject/sample | ↑ | ↓ | ↑ A | ↓ | ↓ | ↓ CCR5+cells | |||||
No difference | ||||||||||||
Controls | ↑ | |||||||||||
Genotype | Homozygous CCR5∆32 | X | X | X | X | |||||||
Heterozygous CCR5∆32 | ||||||||||||
Absent CCR5∆32 | X Px | X Px | ||||||||||
Homozygous WT | X | X Px | ||||||||||
Association/effect of CCR5∆32 | Protective | X M | X | X C | X HBV/HIV | X | ||||||
No association/effect | XS,HBV | |||||||||||
Risk factor/ non-protective | X | X | X | X | X | X | ||||||
Assay(s) used | PCR | X | X | X | X | X | X | X | X | X | X | |
RFLP | X | |||||||||||
Sequencing | X | X | ||||||||||
Immune-based | X | X | X | X | X | X | ||||||
Microscopy | ||||||||||||
Spectroscopy | ||||||||||||
Flow Cytometry | X | X | X | X | X | |||||||
Chromatography | ||||||||||||
MS | ||||||||||||
Other | Meta-analysis | |||||||||||
Parameters | Immune | X | X | X | ||||||||
Metabolic |
Reference | [154] | [155] | [156] | [157] | [158] | [161] | [162] | [169] | [170] | [171] | |
---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | ID | ID | ID | ID | ID | ID | ID | ID | ID | ID | |
Disease | HCV | HCV | HCV | HCV | HCV | CD | CD | H1N1 | H1N1 | H1N1 | |
Population | European | Caucasian | Jewish Israeli | Spanish | British | Mixed | Venezuelan | Mixed | Southern Europe | Brazilian admixed | |
Model | Tissue | Blood | Blood; Tissue | Blood; Tissue | Blood | Blood | Blood | Blood | Blood | Blood | |
CCR5∆32 frequency | Patients | ↑ b | ↓ | ||||||||
No difference | X | X | X | X | X | X | |||||
Controls | |||||||||||
CCR5 levels | Patients/test subject/sample | ↑ Mild disease; ↓ Severe disease | |||||||||
No difference | |||||||||||
Controls | |||||||||||
Genotype | Homozygous CCR5∆32 | X | X | ||||||||
Heterozygous CCR5∆32 | X | X | X | X | X | ||||||
Absent CCR5∆32 | X Px | X | |||||||||
Homozygous WT | |||||||||||
Association/effect of CCR5∆32 | Protective | X C | X b | X C | |||||||
No association/effect | X S | X S,C | X S,P | X C | X | X S | X | X | |||
Risk factor/non-protective | X C | X C | |||||||||
Assay(s) used | PCR | X | X | X | X | X | X | X | X | X | |
RFLP | X | ||||||||||
Sequencing | |||||||||||
Immune-based | X | X | |||||||||
Microscopy | |||||||||||
Spectroscopy | |||||||||||
Flow Cytometry | X | ||||||||||
Chromatography | |||||||||||
MS | |||||||||||
Other | |||||||||||
Parameters | Immune | ||||||||||
Metabolic |
Reference | [172] | [175] | [22] | [176] | [177] | [178] | [179] | [180] | [181] | [182] | |
---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | ID | Cancer | Cancer | Cancer | Cancer | Cancer | Cancer | Cancer | Cancer | Cancer | |
Disease | H1N1 | General | General | General | BC | BC | BC | Carcinomas | PanC | CC | |
Population | Brazilian | N/A | Breast; tumour | Breast; tumour | Iranian | Mixed | N/A | Turkish | Mixed | Indian | |
Model | Tissue; cells | Mice | Cells | Cells | Blood | Meta-analysis | Human cells; Mice | Blood | Blood | Tissue | |
CCR5∆32 frequency | Patients | ↑ b,BC | ↑ b | ||||||||
No difference | X | ||||||||||
Controls | |||||||||||
CCR5 levels | Patients/ test subject/ sample | ↓ | ↑ | ↓ | ↑ | ||||||
No difference | |||||||||||
Controls | |||||||||||
Genotype | Homozygous CCR5∆32 | X | |||||||||
Heterozygous CCR5∆32 | X | X | X | X | |||||||
Absent CCR5∆32 | X KO | X Px,a | |||||||||
Homozygous WT | X | ||||||||||
Association/effect of CCR5∆32 | Protective | X O,P | X | ||||||||
No association/effect | X S.M | X | X S | X Carcinoma | X P,C | ||||||
Risk factor/ non-protective | X | X | X BC | X | X O | ||||||
Assay(s) used | PCR | X | X | X | X | X | X | X | |||
RFLP | X | ||||||||||
Sequencing | X | X | |||||||||
Immune-based | X | X | X | ||||||||
Microscopy | X | ||||||||||
Spectroscopy | X | X | X | ||||||||
Flow Cytometry | X | X | X | X | |||||||
Chromatography | X | ||||||||||
MS | X | X | X | ||||||||
Other | Meta-analysis | ||||||||||
Parameters | Immune | ||||||||||
Metabolic | X | X |
Reference | [183] | [184] | [185] | [186] | [187] | [188] | [189] | [190] | [191] | [192] | |
---|---|---|---|---|---|---|---|---|---|---|---|
Category of Disease | Cancer | Cancer | Cancer | Cancer | Cancer | Cancer | Cancer | Cancer | Cancer | Cancer | |
Disease | CC; HPV | GallC | GasC | GasC | GasC | BlC | PC | PC | PC | AML | |
Population | Swedish | Indian | Japanese | Polish | Chinese | Turkish | Turkish | Brazilian | Australian | Iranian | |
Model | Tissue | Blood | Blood | Blood | Tissue; Cell line | Tissue | Blood | Blood | Blood | Blood | |
CCR5∆32 frequency | Patients | ↑ (HPV+) | ↑ b | ||||||||
No difference | X | ||||||||||
Controls | ↑ b | ||||||||||
CCR5 levels | Patients/test subject/sample | ↑ | ↑ | ||||||||
No difference | |||||||||||
Controls | |||||||||||
Genotype | Homozygous CCR5∆32 | X | X | X | |||||||
Heterozygous CCR5∆32 | X | X | X | X | X | ||||||
Absent CCR5∆32 | X | X Px | |||||||||
Homozygous WT | |||||||||||
Association/effect of CCR5∆32 | Protective | ||||||||||
No association/effect | X S | X | X | X S | X S | ||||||
Risk factor/non-protective | X | X O | X C | X | X | X | |||||
Assay(s) used | PCR | X | X | X | X | X | X | X | X | X | |
RFLP | X | X | X | X | |||||||
Sequencing | X | ||||||||||
Immune-based | X | X | X | ||||||||
Microscopy | |||||||||||
Spectroscopy | |||||||||||
Flow Cytometry | X | ||||||||||
Chromatography | |||||||||||
MS | |||||||||||
Other | |||||||||||
Parameters | Immune | X | |||||||||
Metabolic |
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Rautenbach, A.; Williams, A.A. Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease. Int. J. Mol. Sci. 2020, 21, 1472. https://doi.org/10.3390/ijms21041472
Rautenbach A, Williams AA. Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease. International Journal of Molecular Sciences. 2020; 21(4):1472. https://doi.org/10.3390/ijms21041472
Chicago/Turabian StyleRautenbach, Anandi, and Aurelia A. Williams. 2020. "Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease" International Journal of Molecular Sciences 21, no. 4: 1472. https://doi.org/10.3390/ijms21041472