Patients with early onset of type 1 diabetes have significantly higher GG genotype at position 49 of the CTLA4 gene.
Type 1 diabetes (T1D) is a complex autoimmune disease. Several genetic loci have been implicated in the susceptibility to this illness. Evaluated was the role of the CTLA4 exon 1 A49G polymorphism and its role as a risk factor for T1D in our population. DNA from 190 patients with T1D and their families and 96 control individuals were genotyped for CTLA4 exon 1 polymorphism and human leukocyte antigen (HLA)-DQB1*0201 and *0302 haplotypes by polymerase chain reaction (PCR) amplification-restriction enzyme analysis and PCR amplification that used sequence-specific primers, respectively. Patients were nonobese and <26 years old. The CTLA4 G allele was found to be more frequently present in patients with T1D (32.4%) as compared with its frequency in control individuals (24.5%). The GG genotype was also significantly higher among patients (12.6%) than in controls (4.2%). chi(2) analysis and family-based association studies were performed and suggested the association of CTLA4 exon 1 G polymorphism with T1D (p = 0.0229). Furthermore, in HLA-DQB1*0201-positive patients with T1D, the GG and AA genotypes were higher and lower, respectively, than those found in control individuals. This study suggests that CTLA4 is a candidate susceptibility gene for T1D.
Program for Population Genetics, Harvard School of Public Health, Boston, MA, USA.
Pierre A
PA
Zalloua
Antoine
A
Abchee
Hadia
H
Shbaklo
Tony G
TG
Zreik
Henry
H
Terwedow
Georges
G
Halaby
Sami T
ST
Azar
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003627:Data Interpretation, Statistical; D003922:Diabetes Mellitus, Type 1 / Q000208:ethnology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007861:Lebanon; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D004247:DNA