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P4‐011: A CANDIDATE GENE STUDY OF GENETIC RISK FOR DEMENTIA AND MILD COGNITIVE IMPAIRMENT (MCI) IN WOMEN AGED >65 YEARS: RESULTS FROM THE WOMEN's HEALTH INITIATIVE MEMORY STUDY (WHIMS)
Author(s) -
Driscoll Ira,
Snively Beverly M.,
Espeland Mark A.,
Shumaker Sally A.,
Rapp Stephen R.,
Goveas Joseph S.,
Casanova Ramon,
WactawskiWende Jean,
Manson JoAnn E.,
Rossom Rebecca C.,
Brooks Janet,
Hernandez Dena G.,
Singleton Andrew B.,
Resnick Susan M.
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.1525
Subject(s) - single nucleotide polymorphism , dementia , candidate gene , genome wide association study , international hapmap project , snp , genetics , genetic association , medicine , bioinformatics , oncology , biology , disease , genotype , gene
approach. The genotype data were linked to the age of cognitive decline, estimated as the age at which symptoms of progressive decline were first observed. Kaplan-Meier survival estimates were obtained to test for associations between cognitive decline and APOE and TOMM40 polymorphisms. Results: LD between TOMM40 poly-T lengths of 20 to 29 bases and APOE-e4 was unequivocally shown. Both APOE (p<0.0001) and TOMM40 (p<0.0001) described significant variation in decline, occurring earliest for APOEe4/e4 and TOMM40 poly-T 20-29/20-29. Intermediate cognitive decline was observed for those with a single APOEe4 allele or single poly-T 20-29 TOMM40. Interestingly, the length of TOMM40 poly-T in cases of APOE-e4/e4 was non-random, as no subject with poly-T lengths between 20 and 29 had poly-T lengths of 23-25. Conclusions: Our results demonstrate the tight LD between APOE and TOMM40 polymorphisms and the influence of these polymorphisms on memory decline during aging. The TOMM40 poly-T length may be important in determining TOMM40 protein expression and mitochondrial function, and we hypothesize that 23-25 poly-T lengths may be most damaging to mitochondria.