Change in Plasma Alpha-Tocopherol Associations with Attenuated Pulmonary Function Decline and with CYP4F2 Missense Variation

BackgroundGiven its antioxidant activity, vitamin E is hypothesized to attenuate the age-related decline in pulmonary function. ObjectiveWe investigated the association between change in plasma vitamin E ({Delta}vitE) and pulmonary function decline and examined genetic and non-genetic factors associated with {Delta}vitE. DesignWe studied 1,144 men randomized to vitE in the Selenium and Vitamin E Cancer Prevention Trial. {Delta}vitE was calculated as the difference between baseline and year 3 vitE concentrations measured with gas chromatography-mass spectrometry. Pulmonary function (forced expiratory volume in the first second [FEV1]) was measured longitudinally with spirometry. We genotyped 555 participants (vitE-only arm) using the Illumina MEGAex array. We examined the association of {Delta}vitE with annual change in FEV1 using mixed-effects linear regression. We also examined the association of previously reported genetic and non-genetic factors with {Delta}vitE. ResultsGreater {Delta}vitE was associated with attenuated FEV1 decline, with stronger effects in adherent supplement responders: a 1 SD higher {Delta}vitE (+4 {micro}mol/mmol free-cholesterol-adjusted -tocopherol) attenuated FEV1 decline by [~]8.9 mL/year (P=0.014). This effect size is [~]1/4 of the effect of one year of aging, but in the opposite direction. The {Delta}vitE-FEV1 association was positive in never and current smokers (9.7 and 11.0 mL/year attenuated FEV1 decline, respectively), but there was little to no association in former smokers. Greater {Delta}vitE was associated with lower baseline -tocopherol, higher baseline {gamma}-tocopherol, higher baseline free cholesterol, European ancestry (vs. African ancestry) (all P<0.0001), and the minor allele of a missense variant in CYP4F2 (rs2108622-T) (2.4 {micro}mol/L greater {Delta}vitE; P=0.0032). ConclusionsGreater response to vitE supplementation was associated with attenuated FEV1 decline, and this response was differed by rs2108622 such that individuals with the C allele may need a higher vitE intake dose to reach the same plasma level, compared to the T allele.