BACKGROUND: Histamine intolerance
(HIT) is associated with an excess of histamine because of an impaired function
of the histamine-degrading enzyme diamine oxidase (DAO). The genetic background
of HIT is unknown yet.
METHODS: Case-control association study of all haplotype
tagging and four previously reported DAO SNPs and one HNMT Single nucleotide
polymorphism with symptoms of HIT and DAO serum activity in 484 German
individuals including 285 patients with clinical symptoms of HIT and 199
controls.
RESULTS: Diamine oxidase serum activity was significantly associated
with seven SNPs within the DAO gene. The minor allele at rs2052129, rs2268999,
rs10156191 and rs1049742 increased the risk for a reduced DAO activity whereas
showing a moderate protective effect at rs2071514, rs1049748 and rs2071517 in the
genotypic (P = 2.1 × 10(-8) , 7.6 × 10(-10) , 8.3 × 10(-10) , 0.009, 0.005,
0.00001, 0.006, respectively) and allelic genetic model (P = 2.5 × 10(-11) ,
5.4 × 10(-13) , 8.9 × 10(-13) , 0.00002, 0.006, 0.0003, 0.005, respectively).
Reporter gene assays at rs2052129 revealed a lower promoter activity (P = 0.016)
of the minor allele. DAO mRNA expression in peripheral blood mononuclear cells of
homozygous carriers of the minor allele at rs2052129, rs2268999, rs10156191 was
lower (P = 0.002) than homozygous carriers of the major allele. Diamine oxidase
variants were not associated with the HIT phenotype per se, only with DAO
activity alone and the subgroup of HIT patients displaying a reduced DAO
activity.
CONCLUSIONS: DAO gene variants strongly influence DAO expression and
activity but alone are not sufficient to fully effectuate the potentially
associated disease state of HIT, suggesting an interplay of genetic and
environmental factors.
Source: Allergy 13 April 2011
