Clinical and genetic factors predictive of mortality in early systemic sclerosis.
OBJECTIVE
To investigate the clinical and genetic variables at initial presentation that predict survival in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort.


METHODS
GENISOS is a prospective, observational study of a multiethnic early systemic sclerosis (SSc) cohort. To date, a total of 250 patients have been enrolled. In addition to clinical and laboratory data, electrocardiograms (EKGs), chest radiographs, and pulmonary function tests have been obtained from each patient. A modified Rodnan skin thickness score, HLA class II genotyping, and a Medsger Damage Index also have been collected. We performed multivariable analyses utilizing the Cox regression following a purposeful model building strategy.


RESULTS
The study analyzed 122 white, 47 African American, and 71 Hispanic SSc patients with an average disease duration of 2.6 years at enrollment. At the time of analysis, 52 (20.8%) of the 250 patients had died. In the final multivariable model excluding HLA genes, 7 variables emerged as significant predictors of mortality: age > or =65 years at enrollment, forced vital capacity <50% predicted, clinically significant arrhythmia on EKG, absence of anticentromere antibodies, hypertension, chest radiograph suggestive of pulmonary fibrosis, and low body mass index (BMI). In separate modeling that included HLA genes, HLA alleles DRB1*0802 and DQA1*0501 were significant predictors of mortality in addition to the predictors mentioned above.


CONCLUSIONS
A limited number of variables collected at presentation, including BMI, are able to predict mortality in patients with early SSc. In addition, some of the HLA genes associated with SSc susceptibility are useful for predicting SSc outcome.
Assassi
Shervin
S
University of Texas Health Science Center at Houston, Houston, TX 77030, USA. shervin.assassi@uth.tmc.edu
Del Junco
Deborah
D
Sutter
Kari
K
McNearney
Terry A
TA
Reveille
John D
JD
Karnavas
Andrew
A
Gourh
Pravitt
P
Estrada-Y-Martin
Rosa M
RM
Fischbach
Michael
M
Arnett
Frank C
FC
Mayes
Maureen D
MD
D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology; D015996:Survival Rate; D013781:Texas / Q000453:epidemiology
D006680:HLA Antigens