Associations Of Plasma Selenium Levels,selenoprotein P And Selenoprotein S Genes Polymorphisms With Blood Lipid Levels

Blood lipids are a cluster of biochemical indicators which are changing dynamically,and blood levels of triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)are usually used to reflect blood lipid levels clinically.With changes of dietary pattern and lifestyle,the blood lipid levels among Chinese increased dramatically.The increase of TG,TC,and LDL-C,especially the increase of LDL-C,is a main risk factor of cardiovascular disease.Therefore,identifying factors affecting blood lipid levels and regulating blood lipid levels become an important means to reduce the burden of cardiovascular disease,as well as to promote health.As we all know,environmental factors are associated with blood lipid levels.As the modifiable environment factors,dietary factors are of great significance to the regulation of blood lipid levels.Selenium is an essential trace element ingested mainly through food.Both plasma and serum selenium levels are biomarkers of selenium intake,and epidemiological studies usually measure plasma or serum selenium levels to reflect selenium intake.Selenium is involved in various physiological functions,including oxidation-reduction reactions,inflammatory response,thyroid hormone metabolism,immune function,reproductive function,and so on.Previous studies revealed that high selenium levels might induce oxidative stress and inflammatory injury,and then might have adverse effects on cardiovascular health.However,findings from studies examining associations between selenium levels and blood lipid levels are contradictory.In addition,most studies examining associations between selenium levels and blood lipid levels are cross-sectional,and studies exploring associations between selenium levels and longitudinal changes of blood lipid levels are limited.Exploring associations between selenium levels and longitudinal changes of blood lipid levels is of great importance to predict longitudinal changes of blood lipid levels.Beyond environmental factors,genetic factors also of great significance to blood lipid levels.It is estimated that genetic factors can account for nearly 40-70%of the total variance in blood lipid levels.At present,over 300 genetic loci are identified to be associated with blood lipid levels.However,very few studies have explored genetic loci associated with longitudinal changes in blood lipid levels.In human beings,the physiology functions of selenium are achieved mainly through selenoproteins.Findings from studies suggested that selenoporotein P(SELENOP)and selenoprotein S(SELENOS)might take part in the regulation of blood lipid levels.In addition,several single nucleotide polymorphisms(SNPs)located in SELENOP or SELENOS genes have been associated with cardiovascular diseases.However,no study has examined the associations of SELENOP and SELENOS genes polymorphisms with longitudinal changes in blood lipid levels,as well as the interactions between plasma selenium levels and SELENOP and SELENOS genes polymorphisms in relation to longitudinal changes in blood lipid levels.Hence,based on Tongji-Ezhou cohort,we designed a group of studies among a large-scale of Chinese population to investigate several issues.Firstly,to evaluate cross-sectional associations between plasma selenium levels and blood lipid levels,as well as associations between plasma selenium levels and longitudinal changes in blood lipid levels.Secondly,to examine associations of SELENOP and SELENOS genes polymorphisms with longitudinal changes in blood lipid levels,as well as the interactions between plasma selenium levels and SELENOP and SELENOS genes polymorphisms in relation to longitudinal changes in blood lipid levels.The main content of our study covers the following two parts:Part 1 Associations between plasma selenium levels and blood lipid levelsObjective:To examine cross-sectional associations between plasma selenium levels and blood lipid levels,and associations between plasma selenium levels and longitudinal changes in blood lipid levels.Methods:All participants came from Tongji-Ezhou cohort study.The baseline survey of Tongji-Ezhou cohort study was conducted between 2013 and 2015,and the follow-up survey was conducted between 2016 and 2018,with an average follow-up period of 3 years.Baseline plasma selenium levels were quantified by inductively coupled plasma mass spectrometry(ICP-MS)among 2012 participants.Baseline blood lipid levels were measured according to standard methods among 2012 participants,and blood lipid levels at follow-up were measured among 1961 participants who have participated the follow-up survey.Blood lipid indicators that we have measured include TG,TC,HDL-C,and LDL-C.Cross-sectional and longitudinal analyses were conducted respectively.In cross-sectional analyses,multivariable linear regression model was used to evaluate associations of plasma selenium levels with blood lipid levels.In longitudinal analyses,multivariable linear regression model was used to evaluate associations of plasma selenium levels with longitudinal changes in blood lipid levels,and restricted cubic spline model was used to explore the dose-response relationships between plasma selenium levels and longitudinal changes in blood lipid levels.Results:The median of plasma selenium levels was 92.09?g/L.In cross-sectional analyses,after adjustment for sex,age,body mass index(BMI),smoking status,and so on,results of multivariable linear regression analyses indicated that plasma selenium levels were positively associated with TG,TC,HDL-C and LDL-C(P<0.05),when comparing the highest to the lowest tertiles of plasma selenium levels,TG increased by6.54%(95%CI:0.80%,12.27%;P<0.05),TC increased by 6.31%(95%CI:3.11%,9.52%;P<0.05),HDL-C increased by 3.97%(95%CI:0.86%,7.08%;P<0.05),and LDL-C increased by 9.11%(95%CI:5.35%,12.88%;P<0.05).In longitudinal analyses,after adjustment for sex,age,BMI,smoking status,alcohol drinking status,duration of follow-up,respective baseline blood lipid levels,and so on,results of multivariable linear regression analyses indicated that plasma selenium levels were positively associated with longitudinal changes in TC,LDL-C levels(P<0.05),when comparing the highest to the lowest tertiles of plasma selenium levels,TC increased by 4.41%(95%CI:2.22%,6.59%;P<0.05),LDL-C increased by4.96%(95%CI:1.60%,8.32%;P<0.05).Findings from stratified analyses revealed that the positive association between plasma selenium and longitudinal change in TC was consistent among all subgroups,while the positive association between plasma selenium and longitudinal change in LDL-C was consistent among most subgroups except for women,subjects with BMI?24 kg/m~2,subjects without smoking habit,and subjects with physical activity.Findings from the restricted cubic spline regression analyses demonstrated nonlinear positive relationships between plasma selenium levels and longitudinal changes in TC,LDL-C levels(non-linearity test:P<0.05).Conclusions:Findings from cross-sectional analyses indicated significantly positive associations between plasma selenium levels and TG,TC,HDL-C,and LDL-C levels,and findings from longitudinal analyses indicated significantly positive associations between plasma selenium levels and longitudinal changes in TC,LDL-C levels.Part 2 Interactions between plasma selenium levels and selenoprotein P,selenoprotein S genes polymorphisms in relation to longitudinal changes in blood lipid levelsObjective:To examine the associations of SELENOP and SELENOS genes polymorphisms with longitudinal changes in blood lipid levels,as well as the interactions between plasma selenium levels and SELENOP and SELENOS genes polymorphisms in relation to longitudinal changes in blood lipid levels.Methods:All participants came from Tongji-Ezhou cohort study.The collection of basic information,the quantitative determination of plasma selenium levels,and the measurement of lipid levels at baseline and follow-up have been described in part one.Among subjects included in the longitudinal analyses of part one,1621 subjects have been genotyped on 2 candidate SNPs by using a matrix-assisted laser desorption ionization time-of-flight MS system,these 2 candidate SNPs are SELENOP rs7579 and SELENOS rs4965814.The distribution of gene genotype was analyzed for deviation from Hardy-Weinberg equilibrium by using chi-square goodness of fit test.Multivariable linear regression model was used to examine the associations of SELENOP and SELENOS genes polymorphisms with longitudinal changes in blood lipid levels,likelihood ratio test was used to investigate the interactions between plasma selenium levels and SELENOP and SELENOS genes polymorphisms in relation to longitudinal changes in blood lipid levels.Results:The median of plasma selenium levels was 91.41?g/L.Both SNPs were in accord with Hardy-Weinberg equilibrium among the participants(P-HWE>0.05).Results of multivariable linear regression analyses indicated that the associations of SELENOP rs7579 and SELENOS rs4965814 with longitudinal changes in blood lipid levels were nonsignificant(P>0.05).The interactions between plasma selenium levels and rs7579 in relation to longitudinal changes in TC,HDL-C levels were significant(P for interaction<0.05).When stratifying by tertiles of plasma selenium levels,rs7579was significantly associated with longitudinal changes in TC,HDL-C levels among participants with the highest tertile of plasma selenium levels(P<0.05);In other subgroups,the associations between rs7579 and longitudinal changes in TC,HDL-C levels were non-significant(P>0.05).When comparing rs7579 CT carriers to CC carriers,the longitudinal changes in TC levels in participants with the lowest,middle,and the highest tertiles of plasma selenium levels were 1.34(95%CI:-2.26%,4.94%;P>0.05),0.43%(95%CI:-3.24%,4.09%;P>0.05),and-4.44%(95%CI:-7.77%,-1.11%;P<0.05),respectively;the longitudinal changes in LDL-C levels in participants with the lowest,the second,and the highest tertiles of plasma selenium levels were 3.19%(95%CI:-1.95%,8.34%;P>0.05),3.97%(95%CI:-2.41%,10.34%;P>0.05),and-5.31%(95%CI:-10.38%,-0.24%;P<0.05),respectively.The interactions between plasma selenium levels and SELENOS rs4965814 in relation to longitudinal changes in blood lipid levels were non-significant(P for interaction>0.05).Moreover,findings from the joint-effect analyses revealed that participants with the highest tertile of plasma selenium levels and rs7579 CC genotype had the greatest longitudinal changes in TC,LDL-C levels when comparing with participants with the lowest tertile of plasma selenium levels and rs7579 CC genotype,and the longitudinal changes in TC,LDL-C levels were 7.18%(95%CI:3.91%,10.45%;P<0.05)and 9.66%(95%CI:4.52%,14.80%;P<0.05),respectively.Conclusions:Our findings suggested that in overall participants,the associations of SELENOP rs7579 and SELENOS rs4965814 with longitudinal changes in blood lipid levels were nonsignificant,and the interactions between plasma selenium levels and rs7579 in relation to longitudinal changes in TC,LDL-C levels were significant.In participants with high plasma selenium levels,the associations between rs7579 and longitudinal changes in TC,HDL-C levels were significant.