The neuropeptide genes TAC1, TAC3, TAC4, VIP and PACAP(ADCYAP1), and susceptibility to multiple sclerosis.
The related immunomodulatory neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP; gene symbol ADCYAP1) have recently been proposed as novel therapeutics for the treatment of multiple sclerosis (MS). These neuropeptides, as well as those belonging to the tachykinin family exert pleiotropic effects, many of which are of relevance to central nervous system inflammation. In the present study, we have analysed 14 single nucleotide polymorphisms (SNPs) and 4 microsatellite markers in the VIP, ADCYAP1, TAC3 and TAC4 genes for susceptibility to MS in a case-control collection from Northern Ireland. Following correction for multiple comparisons, we did not find any significant associations between single polymorphic markers or multiple-marker haplotypes and susceptibility to MS. Furthermore, we analysed 2 SNPs in the TAC1 gene in a set of Sardinian trio MS families, based on our previous observation of association of these SNPs with MS in the Northern Irish (Genes Immun. 2005, 6, 265-270). Analysis of these SNPs in the Sardinians was not significant though a similar trend to that originally observed in the Northern Irish was present. Meta-analysis of the Sardinian and Northern Irish TAC1 SNP genotype data revealed a Mantel-Haenszel Common OR Estimate for the TAC1 intron 1 SNP rs2072100 of 0.76 (95% CI 0.63-0.92; P=0.005; A allele) and for the TAC1 promoter SNP rs7793277 of 0.76 (95% CI 0.615-0.95; P=0.014; C allele). Our data advocate a need for further exploration of the TAC1 gene region in MS.
Cunningham
Stephen
S
Applied Genomics Research Group, School of Pharmacy, Center for Cancer Research and Cell Biology (CCRCB), Queen's University of Belfast, and Neurology Department, Royal Victoria Hospital, UK.
O'Doherty
Catherine
C
Patterson
Chris
C
McDonnell
Gavin
G
Hawkins
Stanley
S
Marrosu
Marria G
MG
Vandenbroeck
Koen
K
D004198:Disease Susceptibility; D005838:Genotype; D006801:Humans; D007494:Ireland; D015201:Meta-Analysis as Topic; D009103:Multiple Sclerosis / Q000235:genetics*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D012189:Retrospective Studies; D015320:Tachykinins / Q000235:genetics*; D014660:Vasoactive Intestinal Peptide / Q000235:genetics*
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin; D014660:Vasoactive Intestinal Peptide