Highlights
- •The first study to examine the combined effects of several SNPs within TLR- 4 on PD risk.
- •The first study to examine the interaction between several SNPs within TLR- 4 and alcohol drinking on PD risk.
- •Independent effects of TLR- 4 single nucleotide polymorphism and PD risk.
Abstract
The aim of this study was to investigate the association of several single nucleotide
polymorphisms (SNPs) within Toll-like receptor 4 (TLR4) gene, additional SNP- SNP and gene- alcohol drinking interaction with Parkinson’s
disease (PD) risk. Generalized multifactor dimensionality reduction (GMDR) was used
to screen the best interaction combination among 4 SNPs within TLR4 gene and alcohol drinking. Logistic regression was performed to calculate the ORs
(95%CI) for association between 4 SNPs within TLR4 gene, additional gene- alcohol drinking interaction and PD risk. PD risk was significantly
higher for carriers with the rs7873784- G allele, or with the rs19279149- C allele of within TLR4 gene than those with wild genotypes, adjusted ORs (95%CI) were 0.72 (0.55–0.95) and
0.69 (0.51–0.95). However, we did not find any significant association of rs4986791
and rs11536889 with PD susceptibility after covariates adjustment for age, sex, smoking,
alcohol drinking and BMI. GMDR analysis indicated a significant two-locus model (p = 0.0010)
involving rs1927914 and alcohol drinking, the cross-validation consistency of the
two- locus models was 10/ 10, and the testing accuracy was 60.11%. In logistic regression
analysis, we found that never alcohol- drinkers with rs1927914- TC or CC genotype
within TLR4 gene have the lowest PD risk, compared to drinkers with rs1927914- TT genotype, OR
(95%CI) = 0.42 (0.28–0.61), after covariates adjustment. The rs7873784- G and rs19279149-
C allele within TLR4 gene, interaction between rs1927914 and alcohol drinking were associated with decreased
PD risk.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Clinical NeuroscienceAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Aberrant autophagy and Parkinsonism: does correction rescue from disease progression?.Mol Neurobiol. 2015; 51: 893-9081
- Resveratrol protects from toxin-induced Parkinsonism: plethora of proofs hitherto petty translational value.Mol Neurobiol. 2016; 53: 2751-2760
- Parkinson’s disease in China: prevalence in Beijing, Xian, and Shanghai.Lancet. 2005; 365: 595-597
- Medical management of Parkinson's disease.Pharm Ther. 2008; 33: 590-606
- Polymorphisms in genes involved in the absorption, distribution, metabolism, and excretion of drugs in the Kazakhs of Kazakhstan.BMC Genet. 2016; 17: 23
- Distribution of genetic polymorphisms of genes encoding drug metabolizing enzymes & drug transporters – a review with Indian perspective.Indian J Med Res. 2014; 139: 27-65
- Toll-like receptors and their crosstalk with other innate receptors in infection and immunity.Immunity. 2011; 34: 637-650
- DAMPening inflammation by modulating TLR signalling.Mediators Inflamm. 2010; 2010672395
- Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway.Proc Natl Acad Sci USA. 2003; 100: 8514-8519
- Impact of Toll-like receptor 4 polymorphisms on risk of cancer.Hum Immunol. 2011; 72: 193-206
- Common variants in toll-like receptor 4 confer susceptibility to Alzheimer’s disease in a Han Chinese population.Curr Alzheimer Res. 2012; 9: 458-466
- Sequence variants of toll like receptor 4 and late-onset Alzheimer’s disease.PLoS One. 2012; 7e50771
- Mutations in the gene for toll-like receptor 4 and multiple sclerosis.Tissue Antigens. 2003; 61: 85-88
- Nalls MA, Pankratz N, Lill CM, Do CB, Hernandez DG, Saad M, DeStefano AL, Kara E, Bras J, Sharma M, Schulte C, Keller MF, Arepalli S, Letson C, Edsall C, Stefansson H, Liu X, Pliner H, Lee JH, Cheng R; International Parkinson's Disease Genomics Consortium (IPDGC); Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI); 23 and Me; GenePD; NeuroGenetics Research Consortium (NGRC); Hussman Institute of Human Genomics (HIHG); Ashkenazi Jewish Dataset Investigator; Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE); North American Brain Expression Consortium (NABEC); United Kingdom Brain Expression Consortium (UKBEC); Greek Parkinson's Disease Consortium; Alzheimer Genetic Analysis Group, Ikram MA, Ioannidis JP, Hadjigeorgiou GM, Bis JC, Martinez M, Perlmutter JS, Goate A, Marder K, Fiske B, Sutherland M, Xiromerisiou G, Myers RH, Clark LN, Stefansson K, Hardy JA, Heutink P, Chen H, Wood NW, Houlden H, Payami H, Brice A, Scott WK, Gasser T, Bertram L, Eriksson N, Foroud T, Singleton AB. Large-scale meta- analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nature Genetics 2014; 46(9):989-93.
- The genetic background of Parkinson’s disease: current progress and future prospects.Acta Neurol Scand. 2016; 134: 314-326
- Alcohol intake and risk of Parkinson’s disease: a meta-analysis of observational studies.Mov Disord. 2014; 29: 819-822
- Alcohol use disorders and risk of Parkinson’s disease: findings from a Swedish national cohort study 1972–2008.BMC Neurol. 2013; 13: 190
- Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinicopathological study of 100 cases.J Neurol Neurosurg Psychiatry. 1992; 55: 181-184
- TLR9 21237 T/C and TLR2 2194 to 2174 del polymorphisms and the risk of Parkinson’s disease in the Greek population: a pilot study.Neurol Sci. 2013; 34: 679-682
- Association of TLR4 gene polymorphisms with sporadic Parkinson’s disease in a Han Chinese population.Neurol Sci. 2015; 36: 1659-1665
- Toll-like receptor signalling.Nat Rev Immunol. 2004; 4: 499-511
- Toll-like receptors.Annu Rev Immunol. 2003; 21: 335-376
- Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis.Crit Care. 2003; 7: 23-38
- Biological role of Toll-like receptor-4 in the brain.J Neuroimmunol. 2014; 268: 1-12
- Toll-like receptor 4 is required for a-synuclein dependent activation of microglia and astroglia.Glia. 2013; 61: 349-360
- Detection of copy number changes in genes associated with Parkinson’s disease in Iranian patients.Neurosci Lett. 2013; 551: 75-78
- Effect of ethanol on metabolism of purine bases (hypoxanthine, xanthine, and uric acid).Clin Chim Acta. 2005; 356: 35-57
Article info
Publication history
Published online: December 26, 2018
Accepted:
December 11,
2018
Received:
April 23,
2018
Identification
Copyright
© 2018 Elsevier Ltd. All rights reserved.
