PMID- 26769066
OWN - NLM
STAT- MEDLINE
DCOM- 20180126
LR  - 20220316
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Print)
IS  - 1352-4585 (Linking)
VI  - 22
IP  - 12
DP  - 2016 Oct
TI  - Genetic predictors of relapse rate in pediatric MS.
PG  - 1528-1535
AB  - BACKGROUND: Genetic ancestry, sex, and individual alleles have been associated 
      with multiple sclerosis (MS) susceptibility. OBJECTIVE: To determine whether 
      established risk factors for disease onset are associated with relapse rate in 
      pediatric MS. METHODS: Whole-genome genotyping was performed for 181 MS or 
      high-risk clinically isolated syndrome patients from two pediatric MS centers. 
      Relapses and disease-modifying therapies were recorded as part of continued 
      follow-up. Participants were characterized for 25-hydroxyvitamin D serum status. 
      Ancestral estimates (STRUCTURE v2.3.1), human leukocyte antigen (HLA)-DRB1*15 
      carrier status (direct sequencing), sex, and a genetic risk score (GRS) of 110 
      non-HLA susceptibility single-nucleotide polymorphisms (SNPs) were evaluated for 
      association with relapse rate with Cox and negative binomial regression models. 
      RESULTS: Over 622 patient-years, 408 relapses were captured. Girls had greater 
      relapse rate than boys (incident rate ratio (IRR) = 1.40, 95% confidence interval 
      (CI) = 1.04-1.87, p = 0.026). Participants were genetically diverse; ~40% 
      (N = 75) had <50% European ancestry. HLA-DRB1*15 status modified the association 
      of vitamin D status (p(ixn) = 0.022) with relapse rate (per 10 ng/mL, in DRB1*15+ 
      hazard ratio (HR) = 0.72, 95% CI = 0.58-0.88, p = 0.002; in DRB1*15- HR = 0.96, 
      95% CI = 0.83-1.12, p = 0.64). Neither European ancestry nor GRS was associated 
      with relapse rate. CONCLUSION: We demonstrate that HLA-DRB1*15 modifies the 
      association of vitamin D status with relapse rate. Our findings emphasize the 
      need to pursue disease-modifying effects of MS genes in the context of 
      environmental factors.
CI  - (c) The Author(s), 2016.
FAU - Graves, Jennifer S
AU  - Graves JS
AD  - UCSF Pediatric Multiple Sclerosis Center, San Francisco, CA, USA 
      Jennifer.Graves@ucsf.edu.
FAU - Barcellos, Lisa F
AU  - Barcellos LF
AD  - Genetic Epidemiology and Genomics Lab, School of Public Health, and California 
      Institute for Quantitative Biosciences, University of California-Berkeley, 
      Berkeley, CA, USA.
FAU - Shao, Xiaorong
AU  - Shao X
AD  - Genetic Epidemiology and Genomics Lab, School of Public Health, and California 
      Institute for Quantitative Biosciences, University of California-Berkeley, 
      Berkeley, CA, USA.
FAU - Noble, Janelle
AU  - Noble J
AD  - Children's Hospital Oakland Research Institute, Oakland, CA, USA.
FAU - Mowry, Ellen M
AU  - Mowry EM
AD  - The Multiple Sclerosis Center, Johns Hopkins University, Baltimore, MD, USA.
FAU - Quach, Hong
AU  - Quach H
AD  - Genetic Epidemiology and Genomics Lab, School of Public Health, and California 
      Institute for Quantitative Biosciences, University of California-Berkeley, 
      Berkeley, CA, USA.
FAU - Belman, Anita
AU  - Belman A
AD  - National Pediatric Multiple Sclerosis Center, Stony Brook, NY, USA.
FAU - Casper, T Charles
AU  - Casper TC
AD  - Data Coordinating and Analysis Center, University of Utah, Salt Lake City, UT, 
      USA.
FAU - Krupp, Lauren B
AU  - Krupp LB
AD  - National Pediatric Multiple Sclerosis Center, Stony Brook, NY, USA.
FAU - Waubant, Emmanuelle
AU  - Waubant E
AD  - UCSF Pediatric Multiple Sclerosis Center, San Francisco, CA, USA.
CN  - U.S. Network of Pediatric MS Centers
LA  - eng
GR  - R01 NS071463/NS/NINDS NIH HHS/United States
GR  - K12 HD052163/HD/NICHD NIH HHS/United States
GR  - R01 AI076544/AI/NIAID NIH HHS/United States
GR  - R01 NS049510/NS/NINDS NIH HHS/United States
GR  - R01 ES017080/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160114
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*15 antigen)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Adolescent
MH  - Age of Onset
MH  - Calcitriol/*blood
MH  - Child
MH  - Female
MH  - Follow-Up Studies
MH  - Genotyping Techniques
MH  - HLA-DRB1 Chains/*genetics
MH  - Humans
MH  - Male
MH  - Multiple Sclerosis/*blood/*genetics/*physiopathology
MH  - Recurrence
MH  - Sex Factors
PMC - PMC4945462
MID - NIHMS743331
OTO - NOTNLM
OT  - Genetics
OT  - multiple sclerosis
OT  - outcome measurement
OT  - relapsing/remitting
OT  - vitamin D
EDAT- 2016/01/16 06:00
MHDA- 2018/01/27 06:00
PMCR- 2017/10/01
CRDT- 2016/01/16 06:00
PHST- 2015/07/22 00:00 [received]
PHST- 2015/11/25 00:00 [accepted]
PHST- 2016/01/16 06:00 [pubmed]
PHST- 2018/01/27 06:00 [medline]
PHST- 2016/01/16 06:00 [entrez]
PHST- 2017/10/01 00:00 [pmc-release]
AID - 1352458515624269 [pii]
AID - 10.1177/1352458515624269 [doi]
PST - ppublish
SO  - Mult Scler. 2016 Oct;22(12):1528-1535. doi: 10.1177/1352458515624269. Epub 2016 
      Jan 14.