Multiple sclerosis in twins from continental Italy and Sardinia: a nationwide study.
Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high-prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium-prevalence) and Sardinia (high-prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.62% among MS patients, significantly less than that of the general population. In continental Italy, probandwise concordance was 14.5% (95% confidence interval, 5.1-23.8) for monozygotic and 4.0% (95% confidence interval, 0.8-7.1) for dizygotic twins. Results in Sardinia resemble those in northern populations but in limited numbers. Monozygotic concordance was 22.2% (95% confidence interval, 0-49.3) probandwise, but no concordant dizygotic pairs were identified. A questionnaire on 80 items possibly related to disease cause was administered to 70 twin pairs, 135 sporadic patients, and 135 healthy volunteers. Variables positively (7) or negatively (2) associated with predisposition and concordance in twins largely overlapped and were mainly linked to infection. If compared with previous studies, our data demonstrate that penetrance in twins appears to correlate with MS prevalence. They highlight the relevance of nonheritable variables in Mediterranean areas. The apparent underrepresentation of MS among Italian twins draws attention to protective factors, shared by twins, that may influence susceptibility.
Ristori
Giovanni
G
Neurology and Center for Experimental Neurological Therapy, S. Andrea Hospital, University of Rome La Sapienza, Via di Grottarossa 1035-1039, 00189 Rome, Italy.
Cannoni
Stefania
S
Stazi
Maria Antonietta
MA
Vanacore
Nicola
N
Cotichini
Rodolfo
R
Alfò
Marco
M
Pugliatti
Maura
M
Sotgiu
Stefano
S
Solaro
Claudio
C
Bomprezzi
Roberto
R
Di Giovanni
Simone
S
Figà Talamanca
Lorenzo
L
Nisticò
Lorenza
L
Fagnani
Corrado
C
Neale
Michael C
MC
Cascino
Isabella
I
Giorgi
Gabriele
G
Battaglia
Mario A
MA
Buttinelli
Carla
C
Tosi
Roberto
R
Salvetti
Marco
M
D015331:Cohort Studies; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D014427:Twins