Biomedical subjects

Shuying S Li

Publications and source records attributed to Shuying S Li.

5 recordsLinked to original sources

PubMed2006

Genetic variability, haplotypes, and htSNPs for exons 1 at the human UGT1A locus.

UDP-Glucuronosyltransferases (UGTs) are a superfamily of enzymes responsible for glucuronidation of xenobiotics and endobiotics. Genetic polymorphisms have been identified in the promoter and exonic regions of several UGT genes. The UGT1As on chromosome 2q37 have unique exons 1 but share the remainder of their coding sequence. We screened exon 1 of each of the nine functional UGT1As in Asians (n=46) and Caucasians (n=92) with the aim of determining linkage disequilibrium (LD) and haplotypes across the entire locus in both populations. For polymorphisms in UGT 1A3, 1A4, 1A5, 1A7, and 1A8, we observed significant differences in the allele frequency between the two populations. The haplotype block structure across the UGT1A locus was constructed using all 83 polymorphisms and showed four and five haplotype blocks in Caucasians and Asians, respectively. There was long-distance LD between UGT pairs: 1A8 and 1A10; 1A1 and 1A3; 1A1 and 1A6; 1A6 and 1A7; and 1A7 and 1A9. Whereas both ethnic groups shared some haplotype-tagging SNPs (htSNPs), Caucasians and Asians also had unique htSNPs. This was partly due to the fact that rare variants (<5% allele frequency) were included in our analyses. Haplotypes with frequencies >5% represented only 60% of Caucasian and 65% of Asian UGT1A haplotypes. Differences in haplotype distribution patterns suggest individual and ethnic differences in glucuronidation capacity.

Asian People↗

PubMed2005

FDR-controlling testing procedures and sample size determination for microarrays.

Microarrays are used increasingly to identify genes that are truly differentially expressed in tissues under different conditions. Planning such studies requires establishing a sample size that will ensure adequate statistical power. For microarray analyses, false discovery rate (FDR) is considered to be an appropriate error measure. Several FDR-controlling procedures have been developed. How these procedures perform for such analyses has not been evaluated thoroughly under realistic assumptions. In order to develop a method of determining sample sizes for these procedures, it needs to be established whether these procedures really control the FDR below the pre-specified level so that the determined sample size indeed provides adequate power. To answer this question, we first conducted simulation studies. Our simulation results showed that these procedures do control the FDR at most situations but under-control the FDR when the proportion of positive genes is small, the most likely scenarios. Thus, these existing procedures can overestimate the power and underestimate the sample size. Accordingly, we developed a simulation-based method to provide more accurate estimates for power and sample size.

Algorithms↗

PubMed2005

High concordance of daidzein-metabolizing phenotypes in individuals measured 1 to 3 years apart.

Particular intestinal bacteria are capable of metabolizing the soya isoflavone daidzein to equol and/or O-desmethylangolensin (O-DMA), and the presence of these metabolites in urine after soya consumption are markers of particular intestinal bacteria profiles. Prevalences of equol producers and O-DMA producers are approximately 30-50 % and 80-90 %, respectively, and limited observations have suggested that these daidzein-metabolizing phenotypes are stable within individuals over time. Characterizing stability of these phenotypes is important to understand their potential as markers of long-term exposure to particular intestinal bacteria and their associations with disease risk. We evaluated concordance within an individual for the equol-producer and O-DMA-producer phenotypes measured at two time points (T1, T2), 1-3 years apart. Phenotypes were ascertained by analysing equol and O-DMA using GC-MS in a spot urine sample collected after 3 d soya (source of daidzein) supplementation. In ninety-two individuals without recent (within 3 months before phenotyping) or current antibiotics use, 41 % were equol producers at T1 and 45 % were equol producers at T2, and 90 % were O-DMA producers at T1 and 95 % were O-DMA producers at T2. The percentage agreement for the equol-producer phenotype was 82 and for the O-DMA-producer phenotype was 89. These results indicate that these phenotypes are stable in most individuals over time, suggesting that they provide a useful biomarker for evaluating disease risk associated with harbouring particular intestinal bacteria responsible for, or associated with, the metabolism of the soya isoflavone daidzein.

Anti-Bacterial Agents↗

PubMed2005

Risk factors for colorectal cancer in relation to number and size of aberrant crypt foci in humans.

Several characteristics of aberrant crypt foci (ACF) suggest that they are precursors of colorectal cancer, but the factors that promote or inhibit their growth are largely unknown. We conducted a pilot study to explore whether factors associated with risk of colorectal cancer are also associated with number or size of rectal ACF. Thirty-two U.S. veterans, ages 50 to 80 years, were recruited to undergo magnifying chromoendoscopy for imaging of rectal ACF and colonoscopy for identification of polyps or cancer. Participants completed a questionnaire on cigarette smoking, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and family history of colorectal cancer. Fisher's exact test was used to assess the statistical significance of associations between colorectal cancer risk factors and characteristics of ACF. Cochran-Mantel-Haenszel statistics and polytomous regression were used to test the significance of associations adjusted for age. Participants with a history of adenoma had more ACF than those without (age-adjusted P = 0.02), but the numbers in the two groups overlapped markedly. Older participants had more (P = 0.06) and larger (P = 0.009) ACF than younger participants. No associations were identified between either ACF number or size and cigarette smoking, use of NSAIDs, or family history of colorectal cancer. These findings suggest that persons with adenomas have somewhat more rectal ACF than persons without, and that older age is a risk factor for ACF growth. Future research should be directed toward developing techniques to identify ACF that are likely to progress to cancer and the modifiable factors that promote or inhibit such progression.

Adenoma↗

PubMed2002

Serum beta-glucuronidase activity is inversely associated with plant-food intakes in humans.

Beta-glucuronidase hydrolyzes glucuronide moieties from steroids and xenobiotics, such that circulating glucuronyl conjugates can interact with target tissues. In animal models, dietary constituents can alter beta-glucuronidase activity. In humans, serum beta-glucuronidase activity reflects liver enzyme loss during cell turnover, and thus is a surrogate for hepatic beta-glucuronidase. We recruited 83 men and 120 women, who were nonsmokers, 20-40 y of age, with self-reported vegetable and fruit (V&F) intakes of < or = 2.5 or > or = 4.5 servings/d. Diet was assessed by 3-d food record and serum carotenoids were measured as biomarkers of V&F intake (e.g., servings V&F vs. alpha-carotene; r = 0.47, P = 0.0001). Serum beta-glucuronidase activity (Modified Sigma Units/L), determined in blood samples collected on two consecutive days from fasting subjects, was higher in men than women (mean +/- SEM: 20.4 x 10(3) +/- 1.0 x10(3) and 17.0 x 10(3) +/- 0.6 x 10(3), P = 0.002). beta-Glucuronidase activity (adjusted for sex) was inversely associated with intakes of plant protein, fruit, dietary fiber (r = -0.24 to -0.30; P < 0.001), botanical groupings Cucurbitaceae, Rosaceae, and Leguminosae (r = -0.16 to -0.19; P < 0.05), and serum alpha- and beta-carotene and beta-cryptoxanthin (r = -0.18 to -0.26; P < or = 0.01). Activity was not associated with overall vegetable intake. Although these associations are modest, the data suggest that plant foods, particularly constituents of fruits and fiber-containing foods, may influence human beta-glucuronidase activity in a potentially favorable direction.

Adult↗