PMID- 23266622
OWN - NLM
STAT- MEDLINE
DCOM- 20130325
LR  - 20130204
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 516
IP  - 1
DP  - 2013 Mar 1
TI  - KIR genes and HLA class I ligands in Gaucher disease.
PG  - 53-7
LID - S0378-1119(12)01520-X [pii]
LID - 10.1016/j.gene.2012.12.014 [doi]
AB  - Gaucher disease (GD) is caused by reduced activity of the lysosomal enzyme 
      glucocerebrosidase, which leads to a buildup of glucocerebroside within the cells 
      and chronic stimulation of the immune system. GD is associated with clinical 
      variability even in the same family, which suggests the influence of modifier 
      genes. Natural killer (NK) cells play an important role in the immune response, 
      and their number is decreased in GD. Killer-cell immunoglobulin-like receptors 
      (KIR) regulate the activity of NK cells through an interaction with specific 
      human leukocyte antigen (HLA) class I molecules on target cells. OBJECTIVES: To 
      analyze the variability of KIR genes in a sample of GD patients from Southern 
      Brazil, and look for associations between variants and clinical manifestations. 
      METHODOLOGY: Thirty-one GD patients (24 mild, 4 moderate, and 3 severe) were 
      included in the study. Fifteen KIR genes, HLA-C and HLA-Bw4 were analyzed using 
      SSP-PCR. Clinical, biochemical, and radiological data were collected by means of 
      a chart review. RESULTS/DISCUSSION: Age at symptom onset was associated with 
      KIR2DL2 and KIR2DS2 in combination with the ligand HLA-C1 (p=0.038). Patients who 
      have the HLA-C2 variant appear to have more mono- and polyclonal bands on protein 
      electrophoresis (p=0.007, OR 21.3). There was no between-group significant 
      difference in the frequencies of KIR/HLA variants. CONCLUSION: Although 
      exploratory our data suggest a possible association of KIR/HLA variants and the 
      severity of GD. Further study of KIR/HLA variants is required, as they seem to be 
      a phenotype-modifying factor in this disease.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Vairo, Filippo
AU  - Vairo F
AD  - Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil. 
      fvairo@hcpa.ufrgs.br
FAU - Portela, Pamela
AU  - Portela P
FAU - Salim, Patricia H
AU  - Salim PH
FAU - Jobim, Mariana
AU  - Jobim M
FAU - Netto, Cristina
AU  - Netto C
FAU - Dorneles, Alicia
AU  - Dorneles A
FAU - Mittlestadt, Suzana
AU  - Mittlestadt S
FAU - Jobim, Luiz Fernando
AU  - Jobim LF
FAU - Schwartz, Ida Vanessa D
AU  - Schwartz IV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121221
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-Bw4 antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Ligands)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Brazil
MH  - Female
MH  - Gaucher Disease/*genetics/immunology
MH  - Gene Frequency
MH  - Genes, MHC Class I/*genetics
MH  - Genetic Variation
MH  - Genotype
MH  - HLA-B Antigens/genetics/immunology
MH  - Histocompatibility Antigens Class I/*genetics/immunology
MH  - Humans
MH  - Killer Cells, Natural/metabolism
MH  - Ligands
MH  - Male
MH  - Phenotype
MH  - Receptors, KIR/*genetics/metabolism
MH  - Young Adult
EDAT- 2012/12/26 06:00
MHDA- 2013/03/26 06:00
CRDT- 2012/12/26 06:00
PHST- 2012/06/28 00:00 [received]
PHST- 2012/12/07 00:00 [revised]
PHST- 2012/12/10 00:00 [accepted]
PHST- 2012/12/26 06:00 [entrez]
PHST- 2012/12/26 06:00 [pubmed]
PHST- 2013/03/26 06:00 [medline]
AID - S0378-1119(12)01520-X [pii]
AID - 10.1016/j.gene.2012.12.014 [doi]
PST - ppublish
SO  - Gene. 2013 Mar 1;516(1):53-7. doi: 10.1016/j.gene.2012.12.014. Epub 2012 Dec 21.