Association of cystic fibrosis genetic modifiers with congenital bilateral absence of the vas deferens.
OBJECTIVE
To investigate whether genetic modifiers of cystic fibrosis (CF) lung disease also predispose to congenital bilateral absence of the vas deferens (CBAVD) in association with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. We tested the hypothesis that polymorphisms of transforming growth factor (TGF)-β1 (rs 1982073, rs 1800471) and endothelin receptor type A (EDNRA) (rs 5335, rs 1801708) are associated with the CBAVD phenotype.


METHODS
Genotyping of subjects with clinical CBAVD.


METHODS
Outpatient and hospital-based clinical evaluation.


METHODS
DNA samples from 80 subjects with CBAVD and 51 healthy male controls from various regions of Europe. This is one of the largest genetic studies of this disease to date.


METHODS
None.


METHODS
Genotype analysis.


RESULTS
For single nucleotide polymorphism (SNP) rs 5335, we found increased frequency of the CC genotype among subjects with CBAVD. The difference was significant among Turkish patients versus controls (45.2% vs. 19.4%), and between all cases versus controls (36% vs. 15.7%). No associations between CBAVD penetrance and polymorphisms rs 1982073, rs 1800471, or rs 1801708 were observed.


CONCLUSIONS
Our findings indicate that endothelin receptor type A polymorphism rs 5335 may be associated with CBAVD penetrance. To our knowledge, this is the first study to investigate genetic modifiers relevant to CBAVD.
Havasi
Viktoria
V
Department of Medicine and Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. havasiviktoria@gmail.com
Rowe
Steven M
SM
Kolettis
Peter N
PN
Dayangac
Didem
D
Sahin
Ahmet
A
Grangeia
Ana
A
Carvalho
Filipa
F
Barros
Alberto
A
Sousa
Mario
M
Bassas
Lluis
L
Casals
Teresa
T
Sorscher
Eric J
EJ
D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide; D044022:Receptor, Endothelin A / Q000235:genetics; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014421:Turkey / Q000453:epidemiology; D014564:Urogenital Abnormalities / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D014649:Vas Deferens / Q000002:abnormalities*
C505032:CFTR protein, human; D044022:Receptor, Endothelin A; D053773:Transforming Growth Factor beta1; D019005:Cystic Fibrosis Transmembrane Conductance Regulator