Gene polymorphisms and gene scores linked to low serum carotenoid status and their associations with metabolic disturbance and depressive symptoms in African-American adults.
ABSTRACT: Gene polymorphisms provide a means to obtain unconfounded associations between carotenoids and various health outcomes. In the present study, we tested whether gene polymorphisms and gene scores linked to low serum carotenoid status are related to metabolic disturbance and depressive symptoms in African-American adults residing in Baltimore city, MD, using cross-sectional data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study (age range 30-64 years, n 873-994). We examined twenty-four SNP of various gene loci that were previously shown to be associated with low serum carotenoid status (SNPlcar). Gene risk scores were created: five low specific-carotenoid risk scores (LSCRS: ?-carotene, ?-carotene, lutein+zeaxanthin, ?-cryptoxanthin and lycopene) and one low total-carotenoid risk score (LTCRS: total carotenoids). SNPlcar, LSCRS and LTCRS were entered as predictors for a number of health outcomes. These included obesity, National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome and its components, elevated homeostatic model assessment of insulin resistance, C-reactive protein, hyperuricaemia and elevated depressive symptoms (EDS, Center for Epidemiologic Studies-Depression score ? 16). Among the key findings, SNPlcar were not associated with the main outcomes after correction for multiple testing. However, an inverse association was found between the LTCRS and HDL-cholesterol (HDL-C) dyslipidaemia. Specifically, the ?-carotene and ?-cryptoxanthin LSCRS were associated with a lower odds of HDL-C dyslipidaemia. However, the ?-cryptoxanthin LSCRS was linked to a higher odds of EDS, with a linear dose-response relationship. In summary, gene risk scores linked to low serum carotenoids had mixed effects on HDL-C dyslipidaemia and EDS. Further studies using larger African-American population samples are needed.
Project description:BACKGROUND:Carotenoids have been hypothesized to reduce the risk of many diseases, but associations with intakes or blood concentrations may arise from other constituents of fruit and vegetables. Use of genetic variation in ?-carotene 15,15'-monooxygenase 1 (BCMO1), a key enzyme in provitamin A carotenoid metabolism, as a surrogate for carotenoid exposure may aid in determining the role of carotenoids unconfounded by other carotenoid-containing food constituents, but important variants must be identified. OBJECTIVE:Our goal was to select BCMO1 single nucleotide polymorphisms (SNPs) that predict plasma carotenoid concentrations for use in future epidemiologic studies. DESIGN:We assessed the associations between 224 SNPs in BCMO1 ± 20 kb imputed from the 1000 Genomes Project EUR reference panel with plasma carotenoid and retinol concentrations by using 7 case-control data sets (n = 2344) within the Nurses' Health Study, randomly divided into training (n = 1563) and testing (n = 781) data sets. SNPs were chosen in the training data set through stepwise selection in multivariate linear regression models; ?-coefficients were used as weights in weighted gene scores. RESULTS:Two or 3 SNPs were selected as predictors of ?-carotene, ?-carotene, ?-cryptoxanthin, and lutein/zeaxanthin. In the testing data set, the weighted gene scores were significantly associated with plasma concentrations of the corresponding carotenoid (P = 6.4 × 10?¹², 3.3 × 10?³, 0.02, and 1.8 × 10?¹?, respectively), and concentrations differed by 48%, 15%, 15%, and 36%, respectively, across extreme score quintiles. CONCLUSIONS:SNPs in BCMO1 are associated with plasma carotenoid concentrations. Given adequate sample size, the gene scores may be useful surrogates for carotenoid exposure in future studies.
Project description:Empirical prediction models that weight food frequency questionnaire (FFQ) food items by their relation to nutrient biomarker concentrations may estimate nutrient exposure better than nutrient intakes derived from food composition databases. Carotenoids may especially benefit because contributing foods vary in bioavailability and assessment validity. Our objective was to develop empirical prediction models for the major plasma carotenoids and total carotenoids and evaluate their validity compared with dietary intakes calculated from standard food composition tables. 4180 nonsmoking women in the Nurses' Health Study (NHS) blood subcohort with previously measured plasma carotenoids were randomly divided into training (n = 2787) and testing (n = 1393) subsets. Empirical prediction models were developed in the training subset by stepwise selection from foods contributing ?0.5% to intake of the relevant carotenoid. Spearman correlations between predicted and measured plasma concentrations were compared to Spearman correlations between dietary intake and measured plasma concentrations for each carotenoid. Three to 12 foods were selected for the ?-carotene, ?-carotene, ?-cryptoxanthin, lutein/zeaxanthin, lycopene, and total carotenoids prediction models. In the testing subset, Spearman correlations with measured plasma concentrations for the calculated dietary intakes and predicted plasma concentrations, respectively, were 0.31 and 0.37 for ?-carotene, 0.29 and 0.31 for ?-carotene, 0.36 and 0.41 for ?-cryptoxanthin, 0.28 and 0.31 for lutein/zeaxanthin, 0.22 and 0.23 for lycopene, and 0.22 and 0.27 for total carotenoids. Empirical prediction models may modestly improve assessment of some carotenoids, particularly ?-carotene and ?-cryptoxanthin.
Project description:Among naturally occurring pigments, carotenoids are importantly involved in the photosynthesis of plants and responsible for the coloration of petals and fruits. Osmanthus fragrans Lour., a famous ornamental plant, has many cultivars with different flower color. Petal coloration in O. fragrans mainly depends on the kinds of carotenoids and their contents. To investigate the mechanism of flower coloration in different cultivars, an analysis of phenotypic classification, phytochemistry, as well as the expression of carotenoid metabolism genes based on different groups was performed in the present study. Two main clusters including the orange-red cluster containing Aurantiacus cultivars and the yellowish-white cluster containing the other three cultivar groups were classified using the CIEL?a?b? system. No significant differences in flavonoid contents were observed between these two clusters. However, carotenoids, especially ?-carotene and ?-carotene, were found to have crucial roles in the diversity of floral coloration among the different cultivars. Carotenoid compositions in the petals of cultivars from both clusters consisted of ?-carotene, ?-carotene, ?-cryptoxanthin, ?-cryptoxanthin, lutein, and zeaxanthin, but carotenoid accumulation patterns during the flowering process were different. The petals of the yellowish-white cultivars exhibited high contents of ?-carotene, lutein and ?-carotene, whereas the petals of the orange-red cultivars mainly contained ?-carotene and ?-carotene. The profound diversity in the total carotenoid concentrations in the two clusters was determined by the transcript levels of OfCCD4. Furthermore, the accumulation of upstream products with orange color in orange-red cultivars was partially due to the low expression of OfCHYB, whereas the relatively higher OfCHYB expression in the petals of the yellowish-white cultivars led to higher proportions of lutein, which is yellow. We also found that downregulation of OfLCYE, which encodes ?-ring cyclase, indicated that the carotenoid flux of most cultivars mainly resulted in more ?, ?-branched products. Additionally, carotenoid biosynthesis in green tissues and petals was compared, revealing the tissue specificity of carotenoid accumulation in O. fragrans. Therefore, the effects of multiple genes on carotenoid accumulation give rise to the colorful O. fragrans.
Project description:Provitamin A carotenoids are oxidatively cleaved by β-carotene 15,15'-dioxygenase (BCO1) at the central 15-15' double bond to form retinal (vitamin A aldehyde). Another carotenoid oxygenase, β-carotene 9',10'-oxygenase (BCO2) catalyzes the oxidative cleavage of carotenoids at the 9'-10' bond to yield an ionone and an apo-10'-carotenoid. Previously published substrate specificity studies of BCO2 were conducted using crude lysates from bacteria or insect cells expressing recombinant BCO2. Our attempts to obtain active recombinant human BCO2 expressed in Escherichia coli were unsuccessful. We have expressed recombinant chicken BCO2 in the strain E. coli BL21-Gold (DE3) and purified the enzyme by cobalt ion affinity chromatography. Like BCO1, purified recombinant chicken BCO2 catalyzes the oxidative cleavage of the provitamin A carotenoids β-carotene, α-carotene, and β-cryptoxanthin. Its catalytic activity with β-carotene as substrate is at least 10-fold lower than that of BCO1. In further contrast to BCO1, purified recombinant chicken BCO2 also catalyzes the oxidative cleavage of 9-cis-β-carotene and the non-provitamin A carotenoids zeaxanthin and lutein, and is inactive with all-trans-lycopene and β-apocarotenoids. Apo-10'-carotenoids were detected as enzymatic products by HPLC, and the identities were confirmed by LC-MS. Small amounts of 3-hydroxy-β-apo-8'-carotenal were also consistently detected in BCO2-β-cryptoxanthin reaction mixtures. With the exception of this activity with β-cryptoxanthin, BCO2 cleaves specifically at the 9'-10' bond to produce apo-10'-carotenoids. BCO2 has been shown to function in preventing the excessive accumulation of carotenoids, and its broad substrate specificity is consistent with this.
Project description:A higher dietary intake of carotenoid-rich foods and higher circulating concentrations of carotenoids have been associated with better lung function in cross-sectional studies; however, the longitudinal association between carotenoids and lung function has shown conflicting results.We examined the longitudinal association between serum carotenoids (?-cryptoxanthin, ?-carotene, ?-carotene, lutein/zeaxanthin, and lycopene) and the evolution of lung function.We evaluated our hypothesis in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study. Spirometry testing was conducted at year 0 (1985-1986) and at follow-up in years 2, 5, 10, and 20; serum carotenoids were assayed at years 0 and 15, and diet was assessed at years 0 and 20.Year 0 sum of provitamin A carotenoids and ?-cryptoxanthin concentrations were associated with maximum forced vital capacity (FVC) (P ? 0.01) and forced expiratory volume in 1 s (FEV(1)) (P ? 0.05) (maximum across years 0-10) in linear regression models adjusted for age, race, height, study center, amount of physical activity, smoking status, and BMI. Year 0 lutein/zeaxanthin and lycopene were not associated with maximum lung function. Baseline concentrations of lutein/zeaxanthin, lycopene, sum of the 3 provitamin A carotenoids, ?-carotene, and ?-cryptoxanthin were each inversely associated with a decline from maximum FVC and FEV(1) (P ? 0.04). The sum of provitamin A carotenoids and lycopene remained significant after adjustment for dietary intake related to serum carotenoids (P ? 0.03). The 15-y change in provitamin A carotenoid and lutein/zeaxanthin concentrations was associated with a slower decline from maximum FVC and FEV(1) (P ? 0.04).These findings support an association between serum carotenoid concentrations and a decline in lung function.
Project description:BACKGROUND:Dietary and circulating carotenoids have been inversely associated with breast cancer risk, but observed associations may be due to confounding. Single-nucleotide polymorphisms (SNPs) in ?-carotene 15,15'-monooxygenase 1 (BCMO1), a gene encoding the enzyme involved in the first step of synthesizing vitamin A from dietary carotenoids, have been associated with circulating carotenoid concentrations and may serve as unconfounded surrogates for those biomarkers. We determined associations between variants in BCMO1 and breast cancer risk in a large cohort consortium. METHODS:We used unconditional logistic regression to test four SNPs in BCMO1 for associations with breast cancer risk in 9,226 cases and 10,420 controls from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also tested weighted multi-SNP scores composed of the two SNPs with strong, confirmed associations with circulating carotenoid concentrations. RESULTS:Neither the individual SNPs nor the weighted multi-SNP scores were associated with breast cancer risk [OR (95% confidence interval) comparing extreme quintiles of weighted multi-SNP scores = 1.04 (0.94-1.16) for ?-carotene, 1.08 (0.98-1.20) for ?-carotene, 1.04 (0.94-1.16) for ?-cryptoxanthin, 0.95 (0.87-1.05) for lutein/zeaxanthin, and 0.92 (0.83-1.02) for retinol]. Furthermore, no associations were observed when stratifying by estrogen receptor status, but power was limited. CONCLUSIONS:Our results do not support an association between SNPs associated with circulating carotenoid concentrations and breast cancer risk. IMPACT:Future studies will need additional genetic surrogates and/or sample sizes at least three times larger to contribute evidence of a causal link between carotenoids and breast cancer.
Project description:Carotenoids have shown an interindividual variability that may be due to genetic factors. The only study that has reported heritability of serum ?- and ?-carotene has not considered the environmental component. This study aimed to estimate the contribution of both genetic and common environmental effects to the variance of carotenoid concentrations and to test whether their phenotypic correlations with cardiometabolic risk factors are explained by shared genetic and environmental effects. Plasma carotenoid concentrations (?-carotene, ?-carotene, ?-cryptoxanthin, lutein, lycopene, zeaxanthin, and total carotenoids) of 48 healthy subjects were measured. Heritability estimates of carotenoid concentrations were calculated using the variance component method. Lutein and lycopene showed a significant familial effect (p = 6 × 10-6 and 0.0043, respectively). Maximal heritability, genetic heritability, and common environmental effect were computed for lutein (88.3%, 43.8%, and 44.5%, respectively) and lycopene (45.2%, 0%, and 45.2%, respectively). Significant phenotypic correlations between carotenoid concentrations and cardiometabolic risk factors were obtained for ?-cryptoxanthin, lycopene, and zeaxanthin. Familial resemblances in lycopene concentrations were mainly attributable to common environmental effects, while for lutein concentrations they were attributable to genetic and common environmental effects. Common genetic and environmental factors may influence carotenoids and cardiometabolic risk factors, but further studies are needed to better understand the potential impact on disease development.
Project description:Nutritional quality of most maize varieties is very low due to the lack of lysine and tryptophan and extremely low provitamin A carotenoids including ?-carotene, ?-carotene, and ?-cryptoxanthin. In this study, we report the successful overexpression of the IbOr gene in H145 and H95 inbred maize lines under the control of maize seed-specific promoter globulin 1 (Glo1) for the purpose of improving ?-carotene in maize. The results showed that the total carotenoid and ?-carotene content of all analyzed transgenic maize plants were significantly higher than those of wild-type lines. For H145-IbOr transgenic maize, in the best line (H145-IbOr.10), the total carotenoid and ?-carotene contents were increased up to 10.36- and 15.11-fold, respectively, compared to the wild type (H145-WT). In the case of H95-IbOr transgenic plants, 5.58-fold increase in total carotenoid and 7.63-fold increase in ?-carotene were achieved in the H95-IbOr.6 line compared to nontransgenic plants (H95-WT). In all the transgenic plants derived from the wild-type maize line with less carotenoid content (H145-WT), the content of both total carotenoid and ?-carotene was higher than in transgenic plants derived from the wild-type maize line having more carotenoid content (H95-WT). Our research is the first in successful overexpression of IbOr gene in maize.
Project description:Carotenoids are important coloration molecules and indispensable component of the human diet. And these compounds confer most of the apricot fruit yellow or orange color. In China, fruit of some apricot cultivar present light-yellow color but strong flowery flavor, however, the chemical mechanism remains unknown. Here, carotenoids and aroma volatile apocarotenoids (AVAs) in three skin types of apricot cultivars (orange, yellow, and light-yellow skinned) were determined by HPLC and GC-MS, respectively. And the transcript levels of carotenogenic genes were analyzed by qRT-PCR. The orange-skinned cultivars "Hongyu" and "Danxing" fruit presented the most abundant total carotenoid, ?-carotene and specific ?-carotene contents, and ?-carotene (52-77%) increased to become the dominant carotenoid during fruit ripening. The transcript levels of lycopene ?-cyclase (<i>LCYb</i>) and ?-carotene hydroxylase (<i>CHYb</i>) sharply increased during ripening. The yellow-skinned cultivars "Sulian No. 2" and "Akeyaleke" fruit contained lower levels of total carotenoids and ?-carotene but were rich in phytoene. The light-yellow coloration of "Baixing" and "Luntaixiaobaixing" fruit was attributed to low amounts of total carotenoids, lutein, and neoxanthin and an absence of ?-cryptoxanthin, but high level of aroma volatile apocarotenoids (AVAs) such as ?-ionone were detected in these cultivars fruit, accompanied by low transcript levels of carotene hydroxylase (<i>CYP</i>) and zeaxanthin epoxidase (<i>ZEP</i>) but high levels of carotenoid cleavage dioxygenase 1 (<i>CCD1</i>) and <i>CCD4</i>. Correlation analysis showed that the expression level of <i>CCD1</i> negatively correlated with carotenoid accumulation but positively with AVAs production. These collected results suggest that both carotenoid biosynthesis and degradation are important for apricot coloration and aroma formation. CYP, ZEP, CCD1, and CCD4 may be the key regulation points for carotenoid and AVAs accumulation in apricot fruit, which provide important targets for quality-oriented molecular breeding.
Project description:Carotenoids are naturally occurring pigments that function as vitamin A precursors, antioxidants, anti-inflammatory agents or biomarkers of recent vegetable and fruit intake, and are thus important for population health and nutritional assessment. An assay approach that measures proteins could be more technologically feasible than chromatography, thus enabling more frequent carotenoid status assessment. We explored associations between proteomic biomarkers and concentrations of 6 common dietary carotenoids (?-carotene, ?-carotene, lutein/zeaxanthin, ?-cryptoxanthin, and lycopene) in plasma from 500 6-8 year old Nepalese children. Samples were depleted of 6 high-abundance proteins. Plasma proteins were quantified using tandem mass spectrometry and expressed as relative abundance. Linear mixed effects models were used to determine the carotenoid:protein associations, accepting a false discovery rate of q?<?0.10. We quantified 982 plasma proteins in >10% of all child samples. Among these, relative abundance of 4 were associated with ?-carotene, 11 with lutein/zeaxanthin and 51 with ?-cryptoxanthin. Carotenoid-associated proteins are notably involved in lipid and vitamin A transport, antioxidant function and anti-inflammatory processes. No protein biomarkers met criteria for association with ?-carotene or lycopene. Plasma proteomics may offer an approach to assess functional biomarkers of carotenoid status, intake and biological function for public health application. Original maternal micronutrient trial from which data were derived as a follow-up activity was registered at ClinicalTrials.gov: NCT00115271.