Frequencies of genetic polymorphisms of TLR4 and CD14 and of HLA-DQ genotypes in children with celiac disease, type 1 diabetes mellitus, or both.
OBJECTIVE
Besides the central role of the adaptive immune system, a disturbance of innate immunity is also involved in the pathogenesis of celiac disease (CD). Inasmuch as CD and type 1 diabetes mellitus (T1DM) frequently coexist because of a common genetic predisposition, our aim was to study the frequency of CD14 C-260T and TLR4 A+896G single nucleotide polymorphisms (SNPs) and the distribution of HLA-DQ genotypes in children affected by CD, T1DM, or both.


METHODS
TLR4 and CD14 SNPs were tested by polymerase chain reaction, followed by restriction fragment length polymorphism analysis in 80 children with T1DM, 100 children with CD, and 47 children with both CD and T1DM. Determination of HLA-DQ alleles was done by sequence-specific polymerase chain reaction. Frequencies were compared with those of healthy control children.


RESULTS
The prevalence of the homozygous CD14 C-260TT genotype was significantly (P = 0.0081) lower in children with T1DM but not in those with CD and T1DM, compared with control children. No difference was found in the genotype and allele frequencies of TLR4 between the studied groups. In patients with T1DM, the frequency of the homozygous HLA-DQ8 genotype was significantly higher than in CD, whereas the frequency of homozygous or heterozygous HLA-DQ2 genotypes did not differ from that in control children. In patients with CD, both homozygous and heterozygous HLA-DQ2 genotypes were significantly more frequent than in the control and T1DM groups, and no elevation in the frequency of the HLA-DQ8 genotypes was observed. In patients with T1DM and those with CD and T1DM, the occurrence of HLA-DQ2/8 heterozygosity was significantly higher than in children with CD only and in control children.


CONCLUSIONS
Our results suggest that in patients with T1DM, the CD14 C-260TT homozygous genotype increases the risk for the development of CD. The distribution of HLA-DQ genotype is different in children with CD and T1DM than in children with CD or T1DM only. Determination of the HLA-DQ genotype in children with T1DM may help in estimating the risk for the development of CD.
Dezsofi
A
A
First Department of Pediatrics, Semmelweis University, Hungary. antald@yahoo.com
Szebeni
B
B
Hermann
C S
CS
Kapitány
A
A
Veres
G
G
Sipka
S
S
Körner
A
A
Madácsy
L
L
Korponay-Szabó
I
I
Rajczy
K
K
Arató
A
A
D000293:Adolescent; D002446:Celiac Disease / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D055815:Young Adult
D006683:HLA-DQ Antigens; D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4