Vegetable Signatures Derived from Human Urinary Metabolomic Data in Controlled Feeding Studies.

Examination of changes in urinary metabolomic profiles after vegetable ingestion may lead to new methods of assessing plant food intake. To this regard, we developed a proof-of-principle methodology to identify urinary metabolomic signatures for spinach, celery, and onion. Three feeding studies were conducted. In the first study, healthy individuals were fed with spinach, celery, onion, and no vegetables in four separate experiments with pooled urinary samples for metabolite discovery. The same protocol was used to validate the finding at the individual level in the second study and when feeding all three vegetables simultaneously in the third study. An LC-MS-based metabolomics approach was adopted to search for indicative metabolites from urine samples collected during multiple time periods before and after the meal. Consequently, a total of 1, 9, and 3 nonoverlapping urinary metabolites were associated with the intake of spinach, celery, and onion, respectively. The PCA signature of these metabolites followed a similar "time cycle" pattern, which maximized at approximately 2-4 h after intake. In addition, the metabolite profiles for the same vegetable were consistent across samples, regardless of whether it was consumed individually or in combination. The developed methodology along with the identified urinary metabolomic signatures were potential tools for assessing plant food intake.

SAQC: SNP array quality control.

BACKGROUND: Genome-wide single-nucleotide polymorphism (SNP) arrays containing hundreds of thousands of SNPs from the human genome have proven useful for studying important human genome questions. Data quality of SNP arrays plays a key role in the accuracy and precision of downstream data analyses. However, good indices for assessing data quality of SNP arrays have not yet been developed. RESULTS: We developed new quality indices to measure the quality of SNP arrays and/or DNA samples and investigated their statistical properties. The indices quantify a departure of estimated individual-level allele frequencies (AFs) from expected frequencies via standardized distances. The proposed quality indices followed lognormal distributions in several large genomic studies that we empirically evaluated. AF reference data and quality index reference data for different SNP array platforms were established based on samples from various reference populations. Furthermore, a confidence interval method based on the underlying empirical distributions of quality indices was developed to identify poor-quality SNP arrays and/or DNA samples. Analyses of authentic biological data and simulated data show that this new method is sensitive and specific for the detection of poor-quality SNP arrays and/or DNA samples. CONCLUSIONS: This study introduces new quality indices, establishes references for AFs and quality indices, and develops a detection method for poor-quality SNP arrays and/or DNA samples. We have developed a new computer program that utilizes these methods called SNP Array Quality Control (SAQC). SAQC software is written in R and R-GUI and was developed as a user-friendly tool for the visualization and evaluation of data quality of genome-wide SNP arrays. The program is available online (http://www.stat.sinica.edu.tw/hsinchou/genetics/quality/SAQC.htm).

Lipoprotein lipase variants associated with an endophenotype of hypertension: hypertension combined with elevated triglycerides.

Previously, we observed that young-onset hypertension was independently associated with elevated plasma triglyceride(s) (TG) levels to a greater extent than other metabolic risk factors. Thus, focusing on the endophenotype--hypertension combined with elevated TG--we designed a family-based haplotype association study to explore its genetic connection with novel genetic variants of lipoprotein lipase gene (LPL), which encodes a major lipid metabolizing enzyme. Young-onset hypertension probands and their families were recruited, numbering 1,002 individuals from 345 families. Single-nucleotide polymorphism discovery for LPL, linkage disequilibrium (LD) analysis, transmission disequilibrium tests (TDT), bin construction, haplotype TDT association and logistic regression analysis were performed. We found that the CC- haplotype (i) spanning from intron 2 to intron 4 and the ACATT haplotype (ii) spanning from intron 5 to intron 6 were significantly associated with hypertension-related phenotypes: hypertension (ii, P=0.05), elevated TG (i, P=0.01), and hypertension combined with elevated TG (i, P=0.001; ii, P<0.0001), according to TDT. The risk of this hypertension subtype increased with the number of risk haplotypes in the two loci, using logistic regression model after adjusting within-family correlation. The relationships between LPL variants and hypertension-related disorders were also confirmed by an independent association study. Finally, we showed a trend that individuals with homozygous risk haplotypes had decreased LPL expression after a fatty meal, as opposed to those with protective haplotypes. In conclusion, this study strongly suggests that two LPL intronic variants may be associated with development of the hypertension endophenotype with elevated TG.

A two-stage matched case-control study on multiple hypertensive candidate genes in Han Chinese.

BACKGROUND: Hypertension affects about 1/3 of adults worldwide, ~3.8 million in Taiwan, 160 million in China, and 1 billion worldwide. It is a major risk factor leading to stroke, cardiovascular disease, and end-stage renal disease. In each year, more than 13.5 million deaths are due to hypertension-related diseases worldwide. METHODS: We performed a two-stage association study of hypertension using genotype data of single-nucleotide polymorphisms (SNPs) from 992 young-onset hypertensive cases and 992 matched controls of Han Chinese in Taiwan. A total of 238 SNPs of 36 highly replicated hypertension candidate genes with functional importance were investigated. Association analysis was carried out using conditional logistic regression. RESULTS: We identified two SNPs that were strongly associated with hypertension in both the first and the second stages. The first SNP (rs2301339) is located at guanine nucleotide-binding protein ß3 subunit (GNB3) and the other one (rs17254521) is located at insulin receptor (INSR). CONCLUSIONS: SNP rs2301339 is perfectly linked in linkage disequilibrium (LD) with C825T (rs5443) which has been associated with hypertension in Caucasian, but inconsistent in Asian populations. However, we found that in our sample this SNP has an opposite effect with the previous findings. In summary, this study identified one novel SNP in GNB3 and one novel SNP in INSR that are strongly associated with young-onset hypertension. Due to relatively small sample size, the results should still be interpreted with caution and need to be replicated in other studies.

Vitamin E status and its dietary determinants in Taiwanese--results of the Nutrition and Health Survey in Taiwan 1993-1996.

BACKGROUND: A large proportion of Taiwanese are considered to have inadequate vitamin E intake according to Taiwanese RDA. AIM OF THE STUDY: To evaluate the vitamin E status in Taiwan using biochemical indicators, and to examine the influences of dietary factors. METHODS: The Nutrition and Health Survey in Taiwan 1993-1996 was conducted using a multi-stage sampling scheme. Data of 3614 subjects (1728 males, and 1886 females) aged 4 years and above were included in the current analysis. RESULTS: Females had higher levels of serum alpha-tocopherol than males. Serum level of alpha-tocopherol significantly increased with age and blood lipids (p < 0.001). The prevalence rate of deficiency, assessed by the ratio of serum alpha-tocopherol to cholesterol+triglyceride(TG) < 1.59 micromol/mmol, was 1.4 % for Taiwanese aged 4 and above. The prevalence was 1.02 % for adults. This biochemical profile was superior in women compared to men. The age-serum vitamin E status was U-shaped, being poorest in teenagers. Geographical variation in vitamin E/cholesterol+TG ratio was not apparent across regions. An association was observed between serum vitamin E status and frequency of vitamin E supplements, fresh fruits, and 100 % fruit juices. An association was also seen with dietary intakes of vitamin C and vitamin E assessed by 24-hour recall. CONCLUSION: The prevalence rate of vitamin E deficiency in Taiwan was low. An association was observed between serum vitamin E status and dietary vitamins E and C intakes either from foods or supplements.