IL-10 promoter and IL4-Ralpha gene SNPs are associated with immediate beta-lactam allergy in atopic women.
BACKGROUND
Allergic reactions to beta-lactam antibiotics represent the most frequent cause of immunological drug reactions.


OBJECTIVE
This study evaluates the involvement of genetic susceptibility factors in patients with immediate allergic reactions to beta-lactams. We examined 15 single nucleotide polymorphisms (SNP) of genes coding proteins implicated in immunoglobulin (Ig)E synthesis regulation.


METHODS
We performed a case-control study involving 44 patients with immediate beta-lactam allergy and 44 control subjects, all matched for sex and atopy. Interleukin (IL)-4, IL-13, IL-4Ralpha, signal transducer and activator of transcription 6 (STAT6), interferon (IFN)-gammaR1, IFN-gammaR2 and FcepsilonRIbeta gene polymorphisms were determined using polymerase chain reaction (PCR) restriction fragment length polymorphism, and IL-21R gene and IL-10 promoter polymorphisms by direct sequencing.


RESULTS
Our analysis did not reveal differences in the distribution of the 15 SNPs between allergic patients and controls. However, among atopic subjects, we found two distinct significant associations between immediate beta-lactam allergy in women and the Ile75Val variant of IL-4Ralpha gene (P = 0.012, OR = 5.4, CI: 1.16-27.7), and two linked IL-10 promoter gene polymorphisms, -819C>T and -592 C>A (P = 0.023, OR = 17.5, CI: 1.26-533.07). In contrast, we observed no association in allergic male subjects in the atopic population. Interestingly, the IL-4Ralpha Ile75Val variant could have a paradoxal protective effect in atopic male patients (P = 0.004, OR = 0.07, CI: 0.01-0.66).


CONCLUSIONS
Our findings suggest that polymorphisms in the IL-10 promoter and IL-4Ralpha genes are genetic factors that favour beta-lactam immediate allergies in female patients with atopy.
Guglielmi
L
L
INSERM U454, CHU Arnaud de Villeneuve, Montpellier.
Fontaine
C
C
Gougat
C
C
Avinens
O
O
Eliaou
J-F
JF
Guglielmi
P
P
Demoly
P
P
D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D047090:beta-Lactams / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use
C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D047090:beta-Lactams; D016753:Interleukin-10; D007073:Immunoglobulin E