Περίληψη:
Objective Cerebral venous thrombosis (CVT) is an uncommon form of stroke
affecting mostly young individuals. Although genetic factors are thought
to play a role in this cerebrovascular condition, its genetic etiology
is not well understood. Methods A genome-wide association study was
performed to identify genetic variants influencing susceptibility to
CVT. A 2-stage genome-wide study was undertaken in 882 Europeans
diagnosed with CVT and 1,205 ethnicity-matched control subjects divided
into discovery and independent replication datasets. Results In the
overall case-control cohort, we identified highly significant
associations with 37 single nucleotide polymorphisms (SNPs) within the
9q34.2 region. The strongest association was with rs8176645 (combined p
= 9.15 x 10(-24); odds ratio [OR] = 2.01, 95% confidence interval
[CI] = 1.76-2.31). The discovery set findings were validated across an
independent European cohort. Genetic risk score for this 9q34.2 region
increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20,
p = 2.00 x 10(-16)). SNPs within this region were in strong linkage
disequilibrium (LD) with coding regions of the ABO gene. The ABO blood
group was determined using allele combination of SNPs rs8176746 and
rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI =
2.32-3.52, p = 2.00 x 10(-16)) increased risk of CVT compared with
individuals with blood group O. Interpretation We present the first
chromosomal region to robustly associate with a genetic susceptibility
to CVT. This region more than doubles the likelihood of CVT, a risk
greater than any previously identified thrombophilia genetic risk
marker. That the identified variant is in strong LD with the coding
region of the ABO gene with differences in blood group prevalence
provides important new insights into the pathophysiology of CVT. ANN
NEUROL 2021
Συγγραφείς:
Ken-Dror, Gie
Cotlarciuc, Ioana
Martinelli, Ida
Grandone,
Elvira
Hiltunen, Sini
Lindgren, Erik
Margaglione, Maurizio
and Duchez, Veronique Le Cam
Triquenot, Aude Bagan
Zedde,
Marialuisa
Mancuso, Michelangelo
Ruigrok, Ynte M.
Marjot,
Thomas
Worrall, Brad
Majersik, Jennifer J.
Metso, Tiina M.
and Putaala, Jukka
Haapaniemi, Elena
Zuurbier, Susanna M. and
Brouwer, Matthijs C.
Passamonti, Serena M.
Abbattista, Maria and
Bucciarelli, Paolo
Mitchell, Braxton D.
Kittner, Steven J. and
Lemmens, Robin
Jern, Christina
Pappalardo, Emanuela
Costa,
Paolo
Colombi, Marina
de Sousa, Diana Aguiar
Rodrigues,
Sofia
Canhao, Patricia
Tkach, Aleksander
Santacroce, Rosa
and Favuzzi, Giovanni
Arauz, Antonio
Colaizzo, Donatella and
Spengos, Kostas
Hodge, Amanda
Ditta, Reina
Pezzini,
Alessandro
Debette, Stephanie
Coutinho, Jonathan M.
Thijs,
Vincent
Jood, Katarina
Pare, Guillaume
Tatlisumak, Turgut
and Ferro, Jose M.
Sharma, Pankaj
