Association of killer cell immunoglobulin-like receptors and human leukocyte antigen-C genotypes in South Brazilian with type 1 diabetes.
Type 1 diabetes mellitus (T1D) is a multifactorial and chronic autoimmune disease caused by the deficiency of insulin synthesis and or by its secretion or action defects. Genetic and environmental factors are known to be involved in its pathogenesis. The human leukocyte antigen complex (human leukocyte antigen (HLA)) constitutes the most relevant region contributing with 50% of the inherited risk for T1D. Natural killer cells (NK) are part of the innate immune system recognizing class I HLA molecules on target cells through their membrane receptors, called killer immunoglobulin-like receptors (KIR). The aim of our study is to evaluate the association between the KIR genes and HLA alleles in patients with T1D and healthy controls. Two hundred forty-eight T1D patients and 250 healthy controls were typed for HLA and KIR genes by PCR-SSP. Our results showed an increase of C2 in controls (p = 0.002). The genotype 2DL1/C2+ was also more common in controls (p = 0.001), as well as haplotype association KIR2DL2/DR3/DR4+ and the combination with only DR3+ (p < 0.001; p < 0.001). The maximum protection was seen when KIR2DL2/DR3-were absent when the combination of KIR2DL1/C2+ were present (p < 0.001) and the maximum risk was observed when KIR2DL2/DR3/DR4+ were present in the absence of KIR2DL1/C2- (p = 0.005). Our results confirmed the association of the KIR2DL2/DR3 increasing risk for T1D and suggest a protective role of KIR2DL1/C2.
Jobim
Mariana
M
Department of Immunology, Hospital de Clínicas, Porto Alegre, Brazil; Postgraduate Course in Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. mjobim@hcpa.ufrgs.br
Chagastelles
Pedro
P
Salim
Patrícia H
PH
Portela
Pamela
P
Wilson
Timothy J
TJ
Curti
Alessandra G
AG
Jobim
Maria Regina
MR
João
Daniele A
DA
Nardi
Nance Beyer
NB
Tschiedel
Balduino
B
Jobim
Luiz Fernando
LF
Roesler
Rafael
R
Schwartsmann
Gilberto
G
D000293:Adolescent; D001938:Brazil; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016133:Polymerase Chain Reaction; D054340:Receptors, KIR / Q000235:genetics; D054342:Receptors, KIR2DL1 / Q000235:genetics*; D054345:Receptors, KIR2DL4 / Q000235:genetics; D054347:Receptors, KIR3DL2 / Q000235:genetics
D015236:HLA-C Antigens; C093100:KIR2DL1 protein, human; C515079:KIR2DL4 protein, human; C515084:KIR3DL2 protein, human; C515109:KIR3DL3 protein, human; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054345:Receptors, KIR2DL4; D054347:Receptors, KIR3DL2