Interaction of KIR genes and G1M immunoglobulin allotypes confer susceptibility to type 2 diabetes in Puerto Rican Americans.
The susceptibility to type 2 diabetes (T2D) involves genetic factors. We studied the distribution of KIR and MHC class I ligands phenotype and genotype frequencies, as well as immunoglobulin KM and GM allotype frequencies in a group of patients (N = 95) with T2D and ethnically matched healthy controls (N = 74) with Puerto Rican ethnic background. We found a slight increase of the 2DL3/2DL3 homozygous genotype in T2D. Moreover, the association between 2DL3/2DL3 genotype was significant in the presence of 2DS4 (pC = 0.01). Also, we observed an epistatic effect of the interaction of 2DL3/2DL3, 2DS4 with allele z of G1M in T2D (pC = 0.004, OR = 3.60, 95% CI, 1.62-8.10). This genetic interaction between KIR and G1M allotypes, associated with T2D, was also significant by multiple logistic regression analysis (p < 0.0001, OR = 4.90, 95% CI, 2.12-11.3). We did not detect population stratification using unlinked short tandem repeat (STR) markers, demonstrating that the patients and controls were ethnically matched. Hence, we have demonstrated in this study an epistatic interaction between KIR genes and the G1M allotype that influences the susceptibility to T2D in Puerto Rican Americans. Our findings are important for understanding the autoimmune or innate immune inflammatory-mediated mechanisms involved in the pathogenesis of T2D.
Zuniga
Joaquin
J
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Romero
Viviana
V
Azocar
Jose
J
Stern
Joel N H
JN
Clavijo
Olga
O
Almeciga
Ingrid
I
Encinales
Liliana
L
Avendano
Angel
A
Fridkis-Hareli
Masha
M
Pandey
Janardan P
JP
Yunis
Edmond J
EJ
D002352:Carrier Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006630:Hispanic or Latino / Q000208:ethnology; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014481:United States
D002352:Carrier Proteins; D007126:Immunoglobulin Allotypes; C029702:prolactin-binding protein; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins