Angiotensin-converting enzyme gene does not contribute to genetic susceptibility to systemic sclerosis in European Caucasians.
OBJECTIVE
To determine whether angiotensin-converting enzyme (ACE) polymorphisms including I/D and 2 single-nucleotide polymorphisms (SNP) affect susceptibility to systemic sclerosis (SSc) in a large French Caucasian population.


METHODS
A case-control study was performed in 494 patients with SSc and 280 healthy controls for I/D polymorphism. Two supplementary exonic SNP of ACE gene (rs4309, rs4362) were genotyped in 659 patients with SSc and 511 matched healthy controls. Among the whole SSc population, 453 (67%) patients with SSc had the limited cutaneous subtype, 47 (7%) had precapillary pulmonary arterial hypertension, 209 (32%) had digital ulcers, and 10 (1.5%) had renal crisis. A combined analysis of the available results for ACE I/D genotypes in Caucasians was also performed.


RESULTS
There was no association between the 3 polymorphic markers and SSc for allelic and genotype frequencies. No association was observed for the different vascular subsets of the disease. Haplotype analyses did not detect any association. The lack of association for ACE I/D was confirmed by the combined analysis.


CONCLUSIONS
These results in a large cohort of European Caucasian patients with SSc do not support that the ACE gene is implicated in the pathogenesis of SSc and its vascular damage.
Wipff
Julien
J
Paris Descartes Université, Rhumatologie A, Hôpital Cochin, AP-HP, Paris, France.
Gallier
Guillaume
G
Dieude
Philippe
P
Avouac
Jerome
J
Tiev
Kiet
K
Hachulla
Eric
E
Granel
Brigitte
B
Diot
Elisabeth
E
Sibilia
Jean
J
Mouthon
Luc
L
Meyer
Olivier
O
Kahan
Andre
A
Varret
Mathilde
M
Boileau
Catherine
C
Allanore
Yannick
Y
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015897:Comorbidity; D004252:DNA Mutational Analysis; D005060:Europe / Q000208:ethnology; D005260:Female; D005602:France / Q000208:ethnology; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D007674:Kidney Diseases / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012083:Renin / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D044465:White People
D005819:Genetic Markers; D012083:Renin