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Hsin-Ju Hsieh

Publications and source records attributed to Hsin-Ju Hsieh.

7 recordsLinked to original sources

Allowing for missing data at highly polymorphic genes when testing for maternal, offspring and maternal-fetal genotype incompatibility effects.

Genes can be associated with disease through an individual's inherited genotype, the maternal genotype or the interaction between these two. When the gene is highly polymorphic, it is more difficult to identify the gene's functional role than for less polymorphic loci, because different alleles at the locus may be associated with the disease through separate and joint effects from maternal and offspring genotypes. Family-based studies are used to test genetic associations because of their robustness to population stratification. However, parental genotype data are often missing, and omitting incompletely genotyped families is inefficient. Methods have been proposed to accommodate incomplete families in family-based association studies. They are not easily generalized to allow simultaneous examination of offspring allelic, maternal allelic and maternal-fetal genotype (MFG) incompatibility effects. Since many MFG incompatibility effects occur through matching between maternal and offspring's genotypes, we present an identity-by-state (IBS) framework to incorporate incomplete families in the MFG test when modeling genetic effects produced by a polymorphic gene. Using simulations, we examine the MFG test's performance with incomplete parental genotype data and an IBS framework. The MFG test using the IBS framework is immune to population stratification and efficiently uses information from incomplete families.

Algorithms↗

HLA-B maternal-fetal genotype matching increases risk of schizophrenia.

Schizophrenia and human leukocyte antigen (HLA) matching between couples or between mothers and offspring have independently been associated with prenatal/obstetric complications, including preeclampsia and low birth weight. Here, we report the results of a family-based candidate-gene study that brings together these two disparate lines of research by assessing maternal-fetal genotype matching at HLA-A, -B, and -DRB1 as a risk factor of schizophrenia. We used a conditional-likelihood modeling approach with a sample of 274 families that had at least one offspring with schizophrenia or a related spectrum disorder. A statistically significant HLA-B maternal-fetal genotype-matching effect on schizophrenia was demonstrated for female offspring (P=.01; parameter estimate 1.7 [95% confidence interval 1.22-2.49]). Because the matching effect could be associated with pregnancy complications rather than with schizophrenia per se, these findings are consistent with the neurodevelopmental hypothesis of schizophrenia and with accumulating evidence that the prenatal period is involved in the origins of this disease. Our approach demonstrates how genetic markers can be used to characterize the biology of prenatal risk factors of schizophrenia.

Female↗

Production of ascorbyl palmitate by surfactant-coated lipase in organic media.

The surface of a lipase from Burkholderia cepacia was coated with a nonionic surfactant, propylene glycol monostearate, and was used as a biocatalyst in the production of ascorbic acid in tert-butyl alcohol. The influence of various factors such as the type of surfactant, the pH of the buffer used for coating, the amount of surfactant in the coating, the organic solvent, and the temperature and molar ratio of the substrates used in the reaction on the conversion of ascorbyl palmitate were studied. After 24 h of reaction at 50 degrees C, a conversion of 47% was obtained using an ascorbic acid to palmitic acid molar ratio of 1:6. The native lipase showed only 6% conversion.

Ascorbic Acid↗

The v-MFG test: investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability.

The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

Alleles↗

Synthesis of mixed esters of ascorbic acid using methyl esters of palm and soybean oils.

Mixed esters of ascorbic acid were synthesized using methyl esters of palm and soybean oils as acyl donors, in acetone at 50 degrees C, and catalyzed by Novozym 435. A conversion of 62% was obtained with palm oil methyl ester at an ascorbic acid to acyl donor molar ratio of 1:4; the mixed ester contained 45.89% ascorbyl palmitate, 42.59% ascorbyl oleate and 10.1% ascorbyl linoleate. Acylation with soybean oil methyl ester resulted in 17% conversion, yielding a mixed ester containing 10.08% ascorbyl palmitate, 20.68% ascorbyl oleate, and 64.96% of ascorbyl linoleate. The mixed esters of ascorbic acid can find direct use in food and cosmetics.

Ascorbic Acid↗

Differences in cause-specific mortality between Latino and white adults.

BACKGROUND: Understanding differences in cause-specific mortality between Latinos and whites is important for targeting future public health interventions and research aimed at eliminating health disparities. OBJECTIVES: We sought to determine the contribution of specific causes of death to Latino-white differences in mortality. RESEARCH DESIGN: Using nationally representative data, we estimated cause-specific mortality risks, which were then used in a simulation model to estimate mortality events for a cohort of persons starting at age 25 and followed until death or age 75. SUBJECTS: Subjects were 507,820 Latino and white adults, age 25 or older, who participated in the 1986-1994 National Health Interview Surveys. MEASURES: Outcomes were years of potential life lost before age 75 from specific causes of death and age-specific mortality rate ratios for Latinos compared with whites. RESULTS: Latinos had higher mortality rates than whites before age 45 and similar mortality rates at older ages. Latino women lost 315 (95% confidence interval [CI], 229-2423) more years of potential life (per 1000 persons before the age of 75) than white women and Latino men lost 595 (95% CI, 513-1675) more years than white men. For both men and women, whites lost substantially more years of potential life than Latinos from lung cancer. Homicide, diabetes, HIV, and liver disease contributed most to the excess years of potential life lost among Latino men, and diabetes and HIV contributed most to the excess years of potential life lost among Latino women. CONCLUSIONS: To eliminate health disparities between Latinos and whites, future health policy and public health efforts should target diabetes, homicide, HIV, and liver disease among Latinos and lung cancer among whites.

Acquired Immunodeficiency Syndrome↗

Assessing chronic disease progression using non-homogeneous exponential regression Markov models: an illustration using a selective breast cancer screening in Taiwan.

Previous research on estimation of the progression of chronic disease, from the normal preclinical screen-detectable phase (PCDP) to the final clinical phase, has usually assumed constant transition rates and has rarely addressed how relevant covariates affect multi-state transitions. The present study proposes two non-homogeneous models using the Weibull distribution and piecewise exponential model, together with covariate functions of the proportional hazard form, to tackle these problems. We illustrate the models by application to a selective breast cancer screening programme. The results of the Weibull model yield estimates of scale and shape parameters for annual preclinical incidence rate as 0.0000058 (SE=0.0000019) and 2.4755 (SE=0.1153), the latter being significantly higher than 1. Annual transition rate was estimated as 0.3153 (SE=0.1385). Relative risks for the effects of late age at first pregnancy (AP) and high body mass index (BMI) on preclinical incidence rate were 1.98 and 2.59, respectively. The corresponding figures on the transition from the PCDP to clinical phase were 1.56 and 1.99, respectively. Non-homogeneous Markov models proposed in this study can be easily applied to rates of progression of chronic disease with increasing or decreasing rates with time and to model the effect of relevant covariates on multi-state transition rates.

Adult↗