Variability in histamine receptor genes HRH1, HRH2 and HRH4 in patients with hypersensitivity to NSAIDs.
OBJECTIVE
Histamine plays an important role in the pathogenesis of allergic diseases. Genetic variations in histamine receptors (HRH) may influence the expression of allergic diseases. This study analyzes the association between HRH variants and NSAID hypersensitivity reactions.


METHODS
The authors analyzed copy number variations (CNVs) and common functional SNPs in genes HRH1, HRH2 and HRH4 in 442 unrelated patients with hypersensitivity to NSAIDs and in 414 healthy unrelated controls.


RESULTS
The authors identified, both in patients and control subjects, individuals carrying CNVs in HRH genes. The most common genotype corresponded to two copies of each gene, but carriers of one or three copies of HRH1 (5% of individuals), HRH2 (1.1%) and HRH4 genes (0.9%) were also identified.


CONCLUSIONS
For the first time, we describe CNVs in human HRH genes. Neither common functional SNPs in HRH genes nor CNVs influenced the risk of developing hypersensitivity to NSAIDs.
Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, Avda de la Universidad s/n 10071-Cáceres, Spain.
Pedro
P
Ayuso
Miguel
M
Blanca
José A
JA
Cornejo-García
María José
MJ
Torres
Inmaculada
I
Doña
María
M
Salas
Natalia
N
Blanca-López
Gabriela
G
Canto
Carmen
C
Rondón
Paloma
P
Campo
José J
JJ
Laguna
Javier
J
Fernández
Carmen
C
Martínez
José Ag
JA
Agúndez
Elena
E
García-Martín
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics*; D004342:Drug Hypersensitivity / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011968:Receptors, Histamine / Q000235:genetics*; D011969:Receptors, Histamine H1 / Q000235:genetics*; D011970:Receptors, Histamine H2 / Q000235:genetics*; D000074040:Receptors, Histamine H4; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; C418607:HRH4 protein, human; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D000074040:Receptors, Histamine H4