Abstract Details

Title Melatonin Receptor-1B Genotype, KIBRA Genotype, and Possibly a-Klotho Plasma Level in Women are Associated with Incident Delirium in Elderly Post-surgical Patients

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P6 - Poster Session 6 (12:00 PM-1:00 PM)

Poster/Presentation
Number 10-005

Objective To determine whether genetic polymorphisms in five candidate genes or Klotho protein level are associated with incident delirium in a post-surgical cohort.

Background Delirium is a common geriatric syndrome among elderly inpatients; robust biomarker and genetics data are lacking.

Design/Methods We performed a matched case-control study of 116 patients who underwent non-emergent orthopedic surgeries at a university hospital. 58 subjects with incident delirium measured by the Confusion Assessment Method were matched with subjects without delirium based on age, gender, and pre-operative Telephone Interview for Cognitive Status score. SNP analysis (Quintara Biosciences) included KLOTHO SNP rs9536314, Melatonin Receptor-1B (MTNR1B) SNP rs10830963, KIBRA SNP rs17070145, SIRT-1 SNP rs7896005, and FK506 binding protein 51 (FKBP5) SNP rs1360780, based on published evidence of association with cognition. α-Klotho levels were measured by ELISA. Conditional logistic models stratified on each matched pair were fit and evaluated using the Cochran–Mantel–Haenszel statistic to determine the association between genotype or categorically-defined Klotho protein level and incident delirium.

Results MTNR1B SNP rs10830963 CG or GG genotype is associated with a lower odds of delirium compared to those with CC genotype (OR=0.37(0.15,0.77),p=0.02). KIBRA SNP rs17070145 CT or TT genotype is associated with a lower odds of delirium compared to those with CC genotype (OR=0.31(0.11,0.85),p=0.02), though the association lessened with potential confounders added to the model (OR=0.51(0.24,1.10),p=0.09). There was no significant association found between KLOTHO, SIRT-1, or FKBP5 genotype with delirium. In women, low α-Klotho serum protein level (<450 pg/ml) was associated with higher odds of delirium compared to those with high protein level (OR=2.5(.97,6.44),p=0.06), though this result did not meet statistical significance.

Conclusions Polymorphisms in the Melatonin Receptor-1B and KIBRA gene may play a role in the pathogenesis of delirium. Additionally, low Klotho protein level may be associated with delirium in female patients. Further prospective study in post-surgical hospital population will help elucidate these relationships.

Authors/Disclosures
Mark A. Terrelonge, Jr., MD (University of California, San Francisco) PRESENTER	Dr. Terrelonge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint. Dr. Terrelonge has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for New England Journal of Medicine.
	No disclosure on file
Chris Tang, MD (The Feinstein Institute for Medical Research)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Dena Dubal, MD, PhD (UCSF)	No disclosure on file
Vanja C. Douglas, MD, F�鶹��ýӳ�� (Univ of California, San Francisco)	Dr. Douglas has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Various legal firms. Dr. Douglas has received publishing royalties from a publication relating to health care. Dr. Douglas has received publishing royalties from a publication relating to health care.

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