Chromosome 14 linkage analysis and mutation study of 2 serpin genes in allergic asthmatic families.
BACKGROUND
Genome and chromosome screens reported DNA markers on chromosome 14 linked to allergic asthma or intermediate phenotypes in several populations.


OBJECTIVE
We sought to perform a linkage study on chromosome 14 and a further association study on candidate genes mapped in the region found to be linked to allergic asthma or intermediate phenotypes.


METHODS
The study consisted of a sample of 189 families (847 genotyped individuals) from a restricted geographic area in northeastern Italy. The subjects were characterized for the following phenotypes: allergic asthma, total serum IgE levels, skin prick test responses, and bronchial hyperresponsiveness (BHR) to methacholine. Genotyping was done with 14 DNA markers and 4 polymorphisms in the genes encoding alpha(1)-anti-trypsin and alpha(1)-antichymotrypsin (ACT).


RESULTS
Multipoint analysis indicated a potential linkage of BHR with marker D14S617 (nonparametric linkage z score = 2.32, P =.01). Transmission disequilibrium of Thr -15Ala in the gene encoding ACT was observed with all the phenotypes investigated: allergic asthma, BHR, total IgE levels, or skin prick test responses (P =.041,.02,.0053, or.026, respectively).


CONCLUSIONS
Chromosome 14 screening and transmission disequilibrium testing on the gene encoding ACT suggest that it or a closely located gene may be involved in susceptibility to allergic asthma in the Italian population.
Malerba
G
G
Department of Mother and Child, Biology and Genetics, University of Verona, Strada la Grazie 8, 37134 Verona, Italy.
Patuzzo
C
C
Trabetti
E
E
Lauciello
M C
MC
Galavotti
R
R
Pescollderungg
L
L
Whalen
M B
MB
Zanoni
G
G
Martinati
L C
LC
Boner
A L
AL
Pignatti
P F
PF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D008040:Genetic Linkage; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D000514:alpha 1-Antichymotrypsin / Q000235:genetics*; D000515:alpha 1-Antitrypsin / Q000235:genetics*
D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin