Chromosome 7p linkage and GPR154 gene association in Italian families with allergic asthma.
BACKGROUND
Several genome scans have reported linkage of markers on chromosome 7p with asthma and related phenotypes in different populations. A fine mapping in Finnish and French-Canadian populations has associated the GPR154 gene (also known as G-protein-coupled receptor for asthma susceptibility, GPRA) with elevated IgE or asthma.


OBJECTIVE
To confirm chromosome 7p linkage and candidate gene association in Italian families with atopic asthma.


METHODS
In a two-phase approach, we first performed a linkage analysis of chromosome 7, and then a family-based association study on the GPR154 gene for allergic asthma phenotypes in the Italian population.


RESULTS
The screening of 117 families with 19 microsatellite markers showed potential linkage for elevated IgE (P<0.002 at 22 cM from p-ter), asthma (P<0.005 at 44 cM), or atopy (P<0.005 at 54 cM). In the second phase of the present study, candidate gene GPR154, which is located in the phase one-linked region, was investigated in 211 families with seven single nucleotide polymorphisms (SNPs) that tag most haplotype variability, by the pedigree disequilibrium test. Elevated IgE levels were associated with two GPR154 gene SNPs (SNP 546333, P=0.0046; rs740 347, P=0.006), and with haplotypes in the global test (P=0.013). Haplotype analysis performed in nuclear families having at least 1 asthmatic parent showed a significant association with asthma (P=0.0173), atopy (P=0.0058), SPT (P=0.0025), and bronchial hyper reactivity (P=0.0163).


CONCLUSIONS
These results support a susceptibility locus for asthma and related phenotypes on chromosome 7, and are in agreement with recent reports suggesting that a common susceptibility factor for atopic manifestations in asthma is likely conferred by the locus containing the GPR154 gene.
Malerba
G
G
Department of Mother and Child, Biology and Genetics, University of Verona, Verona, Italy. giovanni.malerba@univr.it
Lindgren
C M
CM
Xumerle
L
L
Kiviluoma
P
P
Trabetti
E
E
Laitinen
T
T
Galavotti
R
R
Pescollderungg
L
L
Boner
A L
AL
Kere
J
J
Pignatti
P F
PF
D001249:Asthma / Q000097:blood / Q000235:genetics*; D016009:Chi-Square Distribution; D002897:Chromosomes, Human, Pair 7; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007558:Italy; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012984:Software; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D044465:White People
D005819:Genetic Markers; C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled; D007073:Immunoglobulin E