Association between Synapsin III gene promoter polymorphisms and multiple sclerosis.
Although multiple sclerosis (MS) is considered to be an inflammatory demyelinating disease, increasing evidence indicates that it is also an axonal pathology; indeed, studies of experimental allergic encephalitis showed that several neuronal proteins such as synapsins take part in the pathogenesis of the axonal dysfunction. Synapsins are a family of abundant neuron-specific phosphoproteins with crucial roles in synaptogenesis and neuronal plasticity. Distinct genes encode the three different isolated proteins (I, II and III); of interest, the gene of synapsin III (SYN3) is located in the chromosome 22q12-q13, a locus close to one of the candidate susceptibility regions (22q13.1) for MS. In the present study we selected two polymorphisms (g.-631C > G and g.-196A > G) within the SYN3 5'-promoter region because of the protein's role and genetic location; we analysed the allele and genotype distributions of these polymorphisms in a selected MS population of southern Italy. An inverse association between MS and the g-631C > G polymorphism was found; indeed, the two polymorphisms were in almost complete linkage disequilibrium and the haplotype analysis showed that the C631/A196 haplotype seemed to confer a significant protection against MS.
Liguori
Maria
M
Institute of Neurological Sciences, National Research Council, Piano Lago di Mangone, Cosenza, Italy.
Cittadella
Rita
R
Manna
Ida
I
Valentino
Paola
P
La Russa
Antonella
A
Serra
Paolo
P
Trojano
Maria
M
Messina
Demetrio
D
Ruscica
Francesca
F
Andreoli
Virginia
V
Romeo
Nelide
N
Livrea
Paolo
P
Quattrone
Aldo
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002648:Child; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009479:Neuropeptides / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016704:Synapsins
D009479:Neuropeptides; D010750:Phosphoproteins; C111812:SYN3 protein, human; D016704:Synapsins