Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis.
Discrepant findings have been reported regarding an association of the apolipoprotein E (APOE) gene with the clinical course of multiple sclerosis (MS). To resolve these discrepancies, we examined common sequence variation in six candidate genes residing in a 380-kb genomic region surrounding and including the APOE locus for an association with MS severity. We genotyped at least three polymorphisms in each of six candidate genes in 1,540 Caucasian MS families (729 single-case and multiple-case families from the United States, 811 single-case families from the UK). By applying the quantitative transmission/disequilibrium test to a recently proposed MS severity score, the only statistically significant (P=0.003) association with MS severity was found for an intronic variant in the Herpes Virus Entry Mediator-B Gene PVRL2. Additional genotyping extended the association to a 16.6 kb block spanning intron 1 to intron 2 of the gene. Sequencing of PVRL2 failed to identify variants with an obvious functional role. In conclusion, the analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports.
Schmidt
S
S
Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA. silke.schmidt@duke.edu
Pericak-Vance
M A
MA
Sawcer
S
S
Barcellos
L F
LF
Hart
J
J
Sims
J
J
Prokop
A M
AM
van der Walt
J
J
DeLoa
C
C
Lincoln
R R
RR
Oksenberg
J R
JR
Compston
A
A
Hauser
S L
SL
Haines
J L
JL
Gregory
S G
SG
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D000483:Alleles; D005091:Exons; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000235:genetics*; D012720:Severity of Illness Index; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D044465:White People
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human