Browsing by Author "Liu, H"

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    Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes
    (JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2015-09) Fang, S; Wang, Y; Chun, YS; Liu, H; Ross, MI; Gershenwald, JE; Cormier, JN; Royal, RE; Lucci, A; Schacherer, CW; Reveille, JD; Chen, W; Sui, D; Bassett, RL; Wang, L-E; Wei, Q; Amos, CI; Lee, JE
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    Genetic variants in the folate metabolic pathway genes predict melanoma-specific survival.
    (The British journal of dermatology, 2020-01-18) Dai, W; Liu, H; Liu, Y; Xu, X; Qian, D; Luo, S; Cho, E; Zhu, D; Amos, CI; Fang, S; Lee, JE; Li, X; Nan, H; Li, C; Wei, Q
    BACKGROUND:Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome-wide association studies (GWAS) have identified some single-nucleotide polymorphisms (SNPs) associated with cutaneous melanoma-specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway. OBJECTIVE:To examine associations between SNPs in folate metabolic pathway genes and CMSS. METHODS:We comprehensively evaluated 2,645 (422 genotyped and 2,223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas M.D. Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow-up Study, in which 95/858 (11.1%) and 48/409 (11.5%) patients died of cutaneous melanoma, respectively. RESULTS:We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta-analysis yielded an allelic hazards ratio of 1.75 (95% confidence interval=1.32-2.32, P=9.96×10-5 ) and 2.05 (1.39-3.01, P=2.84×10-4 ), respectively. The genotype-phenotype correlation analyses provided additional support for biologic plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP-related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS. CONCLUSION:Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated.
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    Genotypic Effects of the TOMM40′523 Variant and APOE on Longitudinal Cognitive Change over 4 Years: The TOMMORROW Study
    (Journal of Prevention of Alzheimer's Disease, 2023-01-01) Zou, H; Luo, S; Liu, H; Lutz, MW; Bennett, DA; Plassman, BL; Welsh-Bohmer, KA
    Background: The 523 poly-T length polymorphism (rs10524523) in TOMM40 has been reported to influence longitudinal cognitive test performance within APOE ε3/3 carriers. The results from prior studies are inconsistent. It is also unclear whether specific APOE and TOMM40 genotypes contribute to heterogeneity in longitudinal cognitive performance during the preclinical stages of AD. Objectives: To determine the effects of these genes on longitudinal cognitive change in early preclinical stages of AD, we used the clinical trial data from the recently concluded TOMMORROW study to examine the effects of APOE and TOMM40 genotypes on neuropsychological test performance. Design: A phase 3, double-blind, placebo-controlled, randomized clinical trial. Setting: Academic affiliated and private research clinics in Australia, Germany, Switzerland, the UK, and the USA. Participants: Cognitively normal older adults aged 65 to 83. Intervention: Pioglitazone tablet. Measurements: Participants from the TOMMORROW trial were stratified based on APOE genotype (APOE ε3/3, APOE ε3/4, APOE ε4/4). APOE ε3/3 carriers were further stratified by TOMM40′523 genotype. The final analysis dataset consists of 1,330 APOE ε3/3 carriers and 7,001 visits. Linear mixed models were used to compare the rates of decline in cognition across APOE groups and the APOE ε3/3 carriers with different TOMM40′523 genotypes. Results: APOE ε3/4 and APOE ε4/4 genotypes compared with the APOE ε3/3 genotype were associated with worse performance on measures of global cognition, episodic memory, and expressive language. Further, over the four years of observation, the APOE ε3/3 carriers with the TOMM40′523-S/S genotype showed better global cognition and accelerated rates of cognitive decline on tests of global cognition, executive function, and attentional processing compared to APOE ε3/3 carriers with TOMM40′523-S/VL and VL/VL genotypes and compared to the APOE ε3/4 and APOE ε4/4 carriers. Conclusions: We suggest that both APOE and TOMM40 genotypes may independently contribute to cognitive heterogeneity in the pre-MCI stages of AD. Controlling for this genetic variability will be important in clinical trials designed to slow the rate of cognitive decline and/or prevent symptom onset in preclinical AD.