Increased frequency of the immunoglobulin enhancer HS1,2 allele 2 in coeliac disease.
BACKGROUND
Coeliac disease (CD) is characterized by increased immunological responsiveness to ingested gliadin in genetically predisposed individuals. This genetic predisposition is not completely defined. A dysregulation of immunoglobulins (Ig) is present in CD: since antiendomysium antibodies (anti-EMA) are of the IgA class. One polymorphic enhancer within the locus control region (LCR) of the immunoglobulin heavy chain cluster at the 3' of the C alpha-1 gene was investigated. The correlation of the penetrance of the four different alleles of the HS1,2-A enhancer of the LCR-1 3' to C alpha-1 in CD patients compared to a control population was analysed.


METHODS
A total of 115 consecutive CD outpatients, on a gluten-free diet, and 248 healthy donors, age- and sex-matched, from the same geographical area were enrolled in the study. HS1,2-A allele frequencies were investigated by nested polymerase chain reaction (PCR).


RESULTS
The frequency of allele 2 of the enhancer HS1,2-A gene was increased by 30.8% as compared to the control frequency. The frequency of homozygosity for allele 2 was significantly increased in CD patients. Crude odds ratio (OR) showed that those with 2/2 and 2/4 (OR 2.63, P < 0.001 and OR 2.01, P = 0.03) have a significantly higher risk of developing the disease. In contrast, allele 1/2 may represent a protective genetic factor against CD (OR 0.52, P = 0.01).


CONCLUSIONS
These data provide further evidence of a genetic predisposition in CD. Because of the Ig dysregulation in CD, the enhancer HS1,2-A may be involved in the pathogenesis.
Frezza
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Department of Biology, Enrico Calef, Tor Vergata University, IT-00133 Rome, Italy. frezza@uniroma2.it
Giambra
V
V
Cianci
R
R
Fruscalzo
A
A
Giufrè
M
M
Cammarota
G
G
Martìnez-Labarga
C
C
Rickards
O
O
Scibilia
G
G
Sferlazzas
C
C
Bartolozzi
F
F
Starnino
S
S
Magazzù
G
G
Gasbarrini
G B
GB
Pandolfi
F
F
D000328:Adult; D002446:Celiac Disease / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005803:Genes, Immunoglobulin; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D019901:Locus Control Region / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic
D005819:Genetic Markers; D007143:Immunoglobulin Heavy Chains