Variations of the perforin gene in patients with multiple sclerosis

G. Cappellano, E. Orilieri, C. Comi, A. Chiocchetti, S. Bocca, E. Boggio, I. S. Bernardone, A. Cometa, R. Clementi, N. Barizzone, S. D'Alfonso, L. Corrado, D. Galimberti, E. Scarpini, F. R. Guerini, D. Caputo, D. Paolicelli, M. Trojano, L. Figà-Talamanca, M. SalvettiF. Perla, M. Leone, F. Monaco, U. Dianzani

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Perforin is involved in cell-mediated cytotoxicity and mutations of its gene (PRF1) cause familial hemophagocytic lymphohistiocytosis (FLH2). PRF1 sequencing in 190 patients with multiple sclerosis and 268 controls detected two FLH2-associated variations (A91V, N252S) in both groups and six novel mutations (C999T, G1065A, G1428A, A1620G, G719A, C1069T) in patients. All together, carriers of these variations were more frequent in patients than in controls (phenotype frequency: 17 vs 9%, P=0.0166; odds ratio (OR)=2.06, 95% confidence interval (CI): 1.13-3.77). Although A91V was the most frequent variation and displayed a trend of association with multiple sclerosis (MS) in the first population of patients and controls (frequency of the 91V allele: 0.076 vs 0.043, P=0.044), we used it as a marker to confirm PRF1 involvement in MS and assessed its frequency in a second population of 966 patients and 1520 controls. Frequency of the 91V allele was significantly higher in patients than in controls also in the second population (0.075 vs 0.058%, P=0.019). In the combined cohorts of 1156 patients and 1788 controls, presence of the 91V allele in single or double dose conferred an OR=1.38 (95% CI=1.10-1.74). These data suggest that A91V and possibly other perforin variations indicate susceptibility to MS.

Original languageEnglish
Pages (from-to)438-444
Number of pages7
JournalGenes and Immunity
Volume9
Issue number5
DOIs
Publication statusPublished - Jul 2008

Fingerprint

Perforin
Multiple Sclerosis
Genes
Gene Frequency
Odds Ratio
Confidence Intervals
Hemophagocytic Lymphohistiocytosis
Mutation
Population Control
Population
Alleles
Phenotype

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Cappellano, G., Orilieri, E., Comi, C., Chiocchetti, A., Bocca, S., Boggio, E., ... Dianzani, U. (2008). Variations of the perforin gene in patients with multiple sclerosis. Genes and Immunity, 9(5), 438-444. https://doi.org/10.1038/gene.2008.35

Variations of the perforin gene in patients with multiple sclerosis. / Cappellano, G.; Orilieri, E.; Comi, C.; Chiocchetti, A.; Bocca, S.; Boggio, E.; Bernardone, I. S.; Cometa, A.; Clementi, R.; Barizzone, N.; D'Alfonso, S.; Corrado, L.; Galimberti, D.; Scarpini, E.; Guerini, F. R.; Caputo, D.; Paolicelli, D.; Trojano, M.; Figà-Talamanca, L.; Salvetti, M.; Perla, F.; Leone, M.; Monaco, F.; Dianzani, U.

In: Genes and Immunity, Vol. 9, No. 5, 07.2008, p. 438-444.

Research output: Contribution to journalArticle

Cappellano, G, Orilieri, E, Comi, C, Chiocchetti, A, Bocca, S, Boggio, E, Bernardone, IS, Cometa, A, Clementi, R, Barizzone, N, D'Alfonso, S, Corrado, L, Galimberti, D, Scarpini, E, Guerini, FR, Caputo, D, Paolicelli, D, Trojano, M, Figà-Talamanca, L, Salvetti, M, Perla, F, Leone, M, Monaco, F & Dianzani, U 2008, 'Variations of the perforin gene in patients with multiple sclerosis', Genes and Immunity, vol. 9, no. 5, pp. 438-444. https://doi.org/10.1038/gene.2008.35
Cappellano G, Orilieri E, Comi C, Chiocchetti A, Bocca S, Boggio E et al. Variations of the perforin gene in patients with multiple sclerosis. Genes and Immunity. 2008 Jul;9(5):438-444. https://doi.org/10.1038/gene.2008.35
Cappellano, G. ; Orilieri, E. ; Comi, C. ; Chiocchetti, A. ; Bocca, S. ; Boggio, E. ; Bernardone, I. S. ; Cometa, A. ; Clementi, R. ; Barizzone, N. ; D'Alfonso, S. ; Corrado, L. ; Galimberti, D. ; Scarpini, E. ; Guerini, F. R. ; Caputo, D. ; Paolicelli, D. ; Trojano, M. ; Figà-Talamanca, L. ; Salvetti, M. ; Perla, F. ; Leone, M. ; Monaco, F. ; Dianzani, U. / Variations of the perforin gene in patients with multiple sclerosis. In: Genes and Immunity. 2008 ; Vol. 9, No. 5. pp. 438-444.
@article{1df90dea1104492cb5e8730bdd737eee,
title = "Variations of the perforin gene in patients with multiple sclerosis",
abstract = "Perforin is involved in cell-mediated cytotoxicity and mutations of its gene (PRF1) cause familial hemophagocytic lymphohistiocytosis (FLH2). PRF1 sequencing in 190 patients with multiple sclerosis and 268 controls detected two FLH2-associated variations (A91V, N252S) in both groups and six novel mutations (C999T, G1065A, G1428A, A1620G, G719A, C1069T) in patients. All together, carriers of these variations were more frequent in patients than in controls (phenotype frequency: 17 vs 9{\%}, P=0.0166; odds ratio (OR)=2.06, 95{\%} confidence interval (CI): 1.13-3.77). Although A91V was the most frequent variation and displayed a trend of association with multiple sclerosis (MS) in the first population of patients and controls (frequency of the 91V allele: 0.076 vs 0.043, P=0.044), we used it as a marker to confirm PRF1 involvement in MS and assessed its frequency in a second population of 966 patients and 1520 controls. Frequency of the 91V allele was significantly higher in patients than in controls also in the second population (0.075 vs 0.058{\%}, P=0.019). In the combined cohorts of 1156 patients and 1788 controls, presence of the 91V allele in single or double dose conferred an OR=1.38 (95{\%} CI=1.10-1.74). These data suggest that A91V and possibly other perforin variations indicate susceptibility to MS.",
author = "G. Cappellano and E. Orilieri and C. Comi and A. Chiocchetti and S. Bocca and E. Boggio and Bernardone, {I. S.} and A. Cometa and R. Clementi and N. Barizzone and S. D'Alfonso and L. Corrado and D. Galimberti and E. Scarpini and Guerini, {F. R.} and D. Caputo and D. Paolicelli and M. Trojano and L. Fig{\`a}-Talamanca and M. Salvetti and F. Perla and M. Leone and F. Monaco and U. Dianzani",
year = "2008",
month = "7",
doi = "10.1038/gene.2008.35",
language = "English",
volume = "9",
pages = "438--444",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Variations of the perforin gene in patients with multiple sclerosis

AU - Cappellano, G.

AU - Orilieri, E.

AU - Comi, C.

AU - Chiocchetti, A.

AU - Bocca, S.

AU - Boggio, E.

AU - Bernardone, I. S.

AU - Cometa, A.

AU - Clementi, R.

AU - Barizzone, N.

AU - D'Alfonso, S.

AU - Corrado, L.

AU - Galimberti, D.

AU - Scarpini, E.

AU - Guerini, F. R.

AU - Caputo, D.

AU - Paolicelli, D.

AU - Trojano, M.

AU - Figà-Talamanca, L.

AU - Salvetti, M.

AU - Perla, F.

AU - Leone, M.

AU - Monaco, F.

AU - Dianzani, U.

PY - 2008/7

Y1 - 2008/7

N2 - Perforin is involved in cell-mediated cytotoxicity and mutations of its gene (PRF1) cause familial hemophagocytic lymphohistiocytosis (FLH2). PRF1 sequencing in 190 patients with multiple sclerosis and 268 controls detected two FLH2-associated variations (A91V, N252S) in both groups and six novel mutations (C999T, G1065A, G1428A, A1620G, G719A, C1069T) in patients. All together, carriers of these variations were more frequent in patients than in controls (phenotype frequency: 17 vs 9%, P=0.0166; odds ratio (OR)=2.06, 95% confidence interval (CI): 1.13-3.77). Although A91V was the most frequent variation and displayed a trend of association with multiple sclerosis (MS) in the first population of patients and controls (frequency of the 91V allele: 0.076 vs 0.043, P=0.044), we used it as a marker to confirm PRF1 involvement in MS and assessed its frequency in a second population of 966 patients and 1520 controls. Frequency of the 91V allele was significantly higher in patients than in controls also in the second population (0.075 vs 0.058%, P=0.019). In the combined cohorts of 1156 patients and 1788 controls, presence of the 91V allele in single or double dose conferred an OR=1.38 (95% CI=1.10-1.74). These data suggest that A91V and possibly other perforin variations indicate susceptibility to MS.

AB - Perforin is involved in cell-mediated cytotoxicity and mutations of its gene (PRF1) cause familial hemophagocytic lymphohistiocytosis (FLH2). PRF1 sequencing in 190 patients with multiple sclerosis and 268 controls detected two FLH2-associated variations (A91V, N252S) in both groups and six novel mutations (C999T, G1065A, G1428A, A1620G, G719A, C1069T) in patients. All together, carriers of these variations were more frequent in patients than in controls (phenotype frequency: 17 vs 9%, P=0.0166; odds ratio (OR)=2.06, 95% confidence interval (CI): 1.13-3.77). Although A91V was the most frequent variation and displayed a trend of association with multiple sclerosis (MS) in the first population of patients and controls (frequency of the 91V allele: 0.076 vs 0.043, P=0.044), we used it as a marker to confirm PRF1 involvement in MS and assessed its frequency in a second population of 966 patients and 1520 controls. Frequency of the 91V allele was significantly higher in patients than in controls also in the second population (0.075 vs 0.058%, P=0.019). In the combined cohorts of 1156 patients and 1788 controls, presence of the 91V allele in single or double dose conferred an OR=1.38 (95% CI=1.10-1.74). These data suggest that A91V and possibly other perforin variations indicate susceptibility to MS.

UR - http://www.scopus.com/inward/record.url?scp=48349133309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48349133309&partnerID=8YFLogxK

U2 - 10.1038/gene.2008.35

DO - 10.1038/gene.2008.35

M3 - Article

C2 - 18496551

AN - SCOPUS:48349133309

VL - 9

SP - 438

EP - 444

JO - Genes and Immunity

JF - Genes and Immunity

SN - 1466-4879

IS - 5

ER -