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Association of mitogen activated protein kinase genetic polymorphism with carotid intima medial thickness (CIMT) in women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS)
Author(s) -
Miller Virginia May,
Petterson Tanya M,
Jeavons Elysia N,
Heit John A,
Harman S Mitchell,
Andrade Mariza
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1134.6
Subject(s) - single nucleotide polymorphism , candidate gene , medicine , intima media thickness , snp , bioinformatics , endocrinology , genetics , biology , genotype , gene , carotid arteries
Menopausal hormone treatments (MHT) may limit progression of CIMT, a measure of atherosclerosis, but pose a risk for ischemic stroke. To test candidate gene variation for an association with CIMT, DNA from 714 women participating in KEEPS, a clinical trial of MHT to prevent progression of atherosclerosis, was genotyped using custom Illumina Infinium iSelect chemistry. Single nucleotide polymorphisms (SNPs; 13,229) were genotyped within 769 genes within the anticoagulant, procoagulant, fibrinolytic or innate immunity pathways. Of these SNPs, 75 were removed due to call rate<0.95, relatedness, duplication, and misidentification; 1275 were removed for quality control. There were 504 ancestry informative markers (AIM). Percent of European ancestry using AIM, age at enrollment and pulse pressure correlated positively with CIMT. Using logistic regression to adjust for these, one SNP (rs2236935 of MAP4K4 on chromosome 2) associated positively with CIMT (p‐value = 5.771e‐06). This gene encodes a protein of the serine/threonine protein kinase family involved in cytokine signaling pathways related to innate immunity, development of type II diabetes, and response to environmental stress. Whether this SNP remains associated with changes in CIMT in women randomized to hormonal treatment in KEEPS remains to be determined. (Supported by grants from the Aurora Foundation, NIH HL90639 and the Mayo Foundation)