Candidate gene analysis of selectin cluster in patients with multiple sclerosis.
Three single nucleotide polymorphisms (SNPs) with a potential impact on the function of selectins (rs6133, rs4987310 and rs5368 substitutions localized in the coding regions of P-sel, L-sel and E-sel, respectively) were analyzed in an Italian population of 165 patients with multiple sclerosis (MS) as compared with 149 controls and in a replication American population of Caucasian descent consisting of 122 patients and 50 controls. No significant differences in either allelic or genotypic frequency in all the SNPs tested were found in the Italian population. A tendency to an increased frequency of the rs6133 T allele was observed in the American population, but applying the Bonferroni correction the significance threshold was not reached. Haploview analysis demonstrated that rs4987310 and rs5368 markers are in strong LD (D' = 0.97) in both populations. Combining the two SNPs, we found no difference in haplotype distribution in patients compared with controls, either in Italian or in American population. Despite the fact that selectins play a role in the pathogenesis of MS and their encoding genes are located in regions associated with the disease, the selectin gene cluster studied likely does not influence the susceptibility to MS in Caucasians.
Fenoglio
Chiara
C
Scalabrini
Diego
D
Piccio
Laura
L
De Riz
Milena
M
Venturelli
Eliana
E
Cortini
Francesca
F
Villa
Chiara
C
Serpente
Maria
M
Parks
Becky
B
Rinker
John
J
Cross
Anne H
AH
Bresolin
Nereo
N
Scarpini
Elio
E
Galimberti
Daniela
D
D000328:Adult; D016000:Cluster Analysis; D004252:DNA Mutational Analysis; D003627:Data Interpretation, Statistical; D019040:E-Selectin / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007558:Italy; D019041:L-Selectin / Q000235:genetics; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D009103:Multiple Sclerosis / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D019007:P-Selectin / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044469:Racial Groups / Q000208:ethnology / Q000235:genetics; D019087:Selectins / Q000235:genetics*; D014481:United States
D019040:E-Selectin; D005819:Genetic Markers; D019007:P-Selectin; D019087:Selectins; D019041:L-Selectin