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Abstract Details

Klotho-VS Heterozygosity is Associated with Lower Risk of Lobar Intracerebral Hemorrhage
Cerebrovascular Disease and Interventional Neurology
Cerebrovascular Disease and Interventional Neurology Posters (7:00 AM-5:00 PM)
089
To test the hypothesis that heterozygosity for KL-VS (KL-VS-Het+) lowers the risk of spontaneous intracerebral hemorrhage (ICH) and the excess in this risk conferred by the APOE epsilon variants.
Two missense variants in the Klotho gene (KL) form the functional haplotype KL-VS. KL-VS-Het+ increases serum levels of Klotho and attenuates the excess risk of Alzheimer’s Disease conferred by APOE epsilon 4.
We conducted a genetic association study using individual level data from European ancestry participants enrolled in 3 case-control studies of ICH. We used the genetic data to determine KL-VS heterozygosity status and APOE epsilon alleles. We tested for association between KL-VS-Het+ and ICH risk via study-specific logistic regression followed by fixed-effects, inverse-variance weighted meta-analysis using I2 to quantify heterogeneity. Given the known biological differences between lobar and non-lobar ICH, we conducted stratified analyses based on location. Additionally, we evaluated the role of KL-VS-Het+ in carriers of APOE epsilon 2 and 4 variants.
A total of 1066 ICH cases (464 lobar and 602 non-lobar) and 1073 controls were included in the study (mean age 69 [SD 14], female sex 919 [47%]). KL-VS-Het+, present in 554 (26%) participants, was associated with a lower risk of ICH (OR 0.81, 95%CI 0.67-0.99; p=0.04) without heterogeneity across studies (I2=0%). Exploratory stratified analyses indicated that KL-VS-Het+ was associated with a lower risk of lobar ICH (OR 0.68, 95%CI 0.52-0.88; p=0.004) but not of non-lobar ICH (OR 0.92, 95%CI 0.73-1.16; p=0.48). In secondary analyses, no significant interaction was found for the association between KL-VS-Het+ and APOE epsilon 2 or 4 carrier status.
KL-VS-Het+ is associated with a lower risk of ICH. This protective association was stronger in lobar hemorrhages. Further research should evaluate these associations in non-Europeans and identify the mediating molecular pathways.
Authors/Disclosures

PRESENTER 		No disclosure on file
Natalia Szejko, MD, PhD Dr. Szejko has nothing to disclose.
No disclosure on file
Audrey Leasure Ms. Leasure has nothing to disclose.
Daniel Woo, MD, FÂ鶹´«Ã½Ó³»­ (University at Buffalo) The institution of Dr. Woo has received research support from NIH.
Carl Langefeld No disclosure on file
Alessandro Biffi, MD (Eli Lilly and Company) Dr. Biffi has received personal compensation for serving as an employee of Eli Lilly And Company. Dr. Biffi has stock in Eli Lilly And Company.
Christopher D. Anderson, MD, PhD, FÂ鶹´«Ã½Ó³»­ (Brigham and Women's Hospital) The institution of Dr. Anderson has received research support from Bayer AG. The institution of Dr. Anderson has received research support from American Heart Association. The institution of Dr. Anderson has received research support from National Institutes of Health. An immediate family member of Dr. Anderson has received publishing royalties from a publication relating to health care.
Jonathan Rosand, MD (Massachusetts General Hospital) Dr. Rosand has received personal compensation for serving as an employee of Massachusetts General Hospital. Dr. Rosand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Rosand has received research support from NIH. The institution of Dr. Rosand has received research support from American Heart Association. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as a Peer reviewer with National Institutes of Health. Dr. Rosand has a non-compensated relationship as a Trustee with Columbia University that is relevant to Â鶹´«Ã½Ó³»­ interests or activities.
Thomas Gill Thomas Gill has nothing to disclose.
Lauren H. Sansing, MD Dr. Sansing has nothing to disclose.
Kevin N. Sheth, MD, FÂ鶹´«Ã½Ó³»­ (Yale UniversityDivision of Neuro and Critical Care) Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zoll. Dr. Sheth has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NControl. Dr. Sheth has received stock or an ownership interest from Astrocyte. Dr. Sheth has received stock or an ownership interest from Alva. The institution of Dr. Sheth has received research support from Biogen. The institution of Dr. Sheth has received research support from Novartis. The institution of Dr. Sheth has received research support from Bard. The institution of Dr. Sheth has received research support from Hyperfine. Dr. Sheth has received intellectual property interests from a discovery or technology relating to health care.
Guido J. Falcone, MD (Yale School of Medicine) The institution of Dr. Falcone has received research support from NIH. The institution of Dr. Falcone has received research support from AHA.