A large multicentre analysis of CTGF -945 promoter polymorphism does not confirm association with systemic sclerosis susceptibility or phenotype.
OBJECTIVE
To conduct a replication study to investigate whether the -945 CTGF genetic variant is associated with systemic sclerosis (SSc) susceptibility or specific SSc phenotype.


METHODS
The study population comprised 1180 patients with SSc and 1784 healthy controls from seven independent case-control sets of European ancestry (Spanish, French, Dutch, German, British, Swedish and North American). The -945 CTGF genetic variant was genotyped using a Taqman 5' allelic discrimination assay.


RESULTS
An independent association study showed in all the case-control cohorts no association of the CTGF -945 polymorphism with SSc susceptibility. These findings were confirmed by a meta-analysis giving a pooled OR = 1.12 (95% CI 0.99 to 1.25), p = 0.06. Investigation of the possible contribution of the -945 CTGF genetic variant to SSc phenotype showed that stratification according to SSc subtypes (limited or diffuse), selective autoantibodies (anti-topoisomerase I or anticentromere) or pulmonary involvement reached no statistically significant skewing.


CONCLUSIONS
The results do not confirm previous findings and suggest that the CTGF -945 promoter polymorphism does not play a major role in SSc susceptibility or clinical phenotype.
Rueda
B
B
Instituto de Parasitologia y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Parque Tecnológico Ciencias de la Salud, Avenida del Conocimiento s/n 18100-Armilla, Granada, Spain.
Simeon
C
C
Hesselstrand
R
R
Herrick
A
A
Worthington
J
J
Ortego-Centeno
N
N
Riemekasten
G
G
Fonollosa
V
V
Vonk
M C
MC
van den Hoogen
F H J
FH
Sanchez-Román
J
J
Aguirre-Zamorano
M A
MA
García-Portales
R
R
Pros
A
A
Camps
M T
MT
Gonzalez-Gay
M A
MA
Gonzalez-Escribano
M F
MF
Coenen
M J
MJ
Lambert
N
N
Nelson
J L
JL
Radstake
T R D J
TR
Martin
J
J
D016022:Case-Control Studies; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012595:Scleroderma, Systemic / Q000235:genetics*
C526317:CCN2 protein, human; D055513:Connective Tissue Growth Factor