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eScholarship provides open access, scholarly publishing services to the University of California and delivers a dynamic research platform to scholars worldwide. Abstract: the American Physiological Society. Prior to the initiation of menopausal hormone treatment (MHT), genetic variations in the innate immunity pathway were found to be associated with carotid artery intima-medial thickness (CIMT) and coronary arterial calcification (CAC) in women (n = 606) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these associations is unknown. The association of treatment outcomes with variation in the same 764 candidate genes was evaluated in the same KEEPS participants 4 yr after randomization to either oral conjugated equine estrogens (0.45 mg/day), transdermal 17β-estradiol (50 μg/day), each with progesterone (200 mg/day) for 12 days each month, or placebo pills and patch. Twenty SNPs within the innate immunity pathway most related with CIMT after 4 yr were not among those associated with CIMT prior to MHT. In 403 women who completed the study in their assigned treatment group, single nucleotide polymorphisms (SNPs) within the innate immunity pathway were found to alter the treatment effect on 4 yr change in CIMT (i.e., significant interaction between treatment and genetic variation in the innate immunity pathway; P < 0.001). No SNPs by treatment effects were observed with changes of CAC > 5 Agatston units after 4 yr. Results of this study suggest that hormonal status may interact with genetic variants to influence cardiovascular phenotypes, specifically, the pharmacogenomic effects within the innate immunity pathway for CIMT. Abstract 45 46 Background: Prior to the initiation of menopausal hormone treatment (MHT), genetic variations 47 in the innate immunity pathway were found to be associated with carotid artery intima-medial 48 thickness (CIMT) and coronary arterial calcification (CAC) in women (n=606) enrolled in the 49 Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these 50 associations is unknown. 51 Methods: The association of treatment outcomes with variation in the same 764 candidate 52 genes was evaluated in same KEEPS participants four years after randomization to either oral 53 conjugated equine estrogens (0.45 mg/day), transdermal 17β estradiol (50 µg/day), each with 54 progesterone (200 mg/day) for 12 days each month, or placebo pills and patch. 55 Results: Twenty SNPs within the innate immunity pathway most related with CIMT after 4 years 56 were not among those associated with CIMT prior to MHT. In 403 women who completed the 57 study in their assigned treatment group, SNPs within the innate immunity pathway were found to 58 alter the treatment effect on 4-year change in CIMT (i.e. significant interaction between 59 treatment and genetic variation in the innate immunity pathway; p<0.001). No SNPs by 60 treatment effects were observed with changes of CAC >5 Agatston Units after 4 years. 61 Conclusion: Results of this study suggest that hormonal status may interact with genetic 62 variants to influence cardiovascular phenotypes, specifically, the pharmacogenomic effects within the innate immunity pathway for CIMT. by Wilcoxon signed ranks test. HOMA-IR Homeostasis Model Assessment