Browsing by Subject "gene polymorphism"

Now showing 1 - 3 of 3
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    Association between Aldehyde Dehydrogenase 2 Glu504Lys Polymorphism and Alcoholic Liver Disease
    (Elsevier, 2018) Chang, Binxia; Hao, Shuli; Zhang, Longyu; Gao, Miaomiao; Sun, Ying; Huang, Ang; Teng, Guangju; Li, Baosen; Crabb, David W.; Kusumanchi, Praveen; Wang, Li; Liangpunsakul, Suthat; Zou, Zhengsheng; Medicine, School of Medicine
    Background Only a subset of patients with excessive alcohol use develop alcoholic liver disease (ALD); though the exact mechanism is not completely understood. Once ingested, alcohol is metabolized by 2 key oxidative enzymes, alcohol (ADH) and aldehyde dehydrogenase (ALDH). There are 2 major ALDH isoforms, cytosolic and mitochondrial, encoded by the aldehyde ALDH1 and ALDH2 genes, respectively. The ALDH2 gene was hypothesized to alter genetic susceptibility to alcohol dependence and alcohol-induced liver diseases. The aim of this study is to determine the association between aldehyde dehydrogenase 2 (rs671) glu504lys polymorphism and ALD. Methods ALDH2 genotype was performed in 535 healthy controls and 281 patients with ALD. Results The prevalence of the common form of the SNP rs671, 504glu (glu/glu) was significantly higher in patients with ALD (95.4%) compared to that of controls (73.7%, p<0.0001). Among controls, 23.7% had heterozygous (glu/lys) genotype when compared to 4.6% in those with ALD (OR 0.16, 95%CI 0.09–0.28). The allele frequency for 504lys allele in patients with ALD was 2.3%; compared to 14.5% in healthy controls (OR 0.13, 95%CI 0.07–0.24). Conclusions Patients with ALDH2 504lys variant were less associated with ALD compared to those with ALDH2 504glu using both genotypic and allelic analyses.
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    A regulatory insertion-deletion polymorphism in the FADS gene cluster influences PUFA and lipid profiles among Chinese adults: a population-based study
    (Oxford, 2018-06) Li, Peiqin; Zhao, Jing; Kothapalli, Kumar S. D.; Li, Xiang; Li, Hui; Han, Yuxuan; Mi, Shengquan; Zhao, Wenhua; Li, Qizhai; Zhang, Hong; Song, Yiqing; Brenna, J. Thomas; Gao, Ying; Epidemiology, School of Public Health
    Background Arachidonic acid (AA) is the major polyunsaturated fatty acid (PUFA) substrate for potent eicosanoid signaling to modulate inflammation and thrombosis and is controlled in part by tissue abundance. Fatty acid desaturase 1 (FADS1) catalyzes synthesis of omega-6 (n–3) AA and n–3 eicosapentaenoic acid (EPA). The rs66698963 polymorphism, a 22-base pair (bp) insertion-deletion 137 bp downstream of a sterol regulatory element in FADS2 intron 1, mediates expression of FADS1 in vitro, as well as exerting positive selection in several human populations. The associations between the polymorphism rs66698963 and plasma PUFAs as well as disease phenotypes are unclear. Objective This study aimed to evaluate the relation between rs66698963 genotypes and plasma PUFA concentrations and blood lipid profiles. Design Plasma fatty acids were measured from a single sample obtained at baseline in 1504 healthy Chinese adults aged between 35 and 59 y with the use of gas chromatography. Blood lipids were measured at baseline and a second time at the 18-mo follow-up. The rs66698963 genotype was determined by using agarose gel electrophoresis. Linear regression and logistic regression analyses were performed to assess the association between genotype and plasma PUFAs and blood lipids. Results A shift from the precursors linoleic acid and α-linolenic acid to produce AA and EPA, respectively, was observed, consistent with FADS1 activity increasing in the order of genotypes D/D to I/D to I/I. For I/I compared with D/D carriers, plasma concentrations of n–6 AA and the ratio of AA to n–3 EPA plus docosahexaenoic acid (DHA) were 57% and 32% higher, respectively. Carriers of the deletion (D) allele of rs66698963 tended to have higher triglycerides (β = 0.018; SE: 0.009; P = 0.05) and lower HDL cholesterol (β = −0.008; SE: 0.004; P = 0.02) than carriers of the insertion (I) allele. Conclusions The rs66698963 genotype is significantly associated with AA concentrations and AA to EPA+DHA ratio, reflecting basal risk of inflammatory and related chronic disease phenotypes, and is correlated with the risk of dyslipidemia.
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    Uromodulin (Tamm–Horsfall protein): guardian of urinary and systemic homeostasis
    (Oxford, 2020-01) Micanovic, Radmila; LaFavers, Kaice; Garimella, Pranav S.; Wu, Xue-Ru; El-Achkar, Tarek M.; Medicine, School of Medicine
    Biology has taught us that a protein as abundantly made and conserved among species as Tamm–Horsfall protein (THP or uromodulin) cannot just be a waste product serving no particular purpose. However, for many researchers, THP is merely a nuisance during urine proteome profiling or exosome purification and for clinicians an enigmatic entity without clear disease implications. Thanks to recent human genetic and correlative studies and animal modeling, we now have a renewed appreciation of this highly prevalent protein in not only guarding urinary homeostasis, but also serving as a critical mediator in systemic inter-organ signaling. Beyond a mere barrier that lines the tubules, or a surrogate for nephron mass, mounting evidence suggests that THP is a multifunctional protein critical for modulating renal ion channel activity, salt/water balance, renal and systemic inflammatory response, intertubular communication, mineral crystallization and bacterial adhesion. Indeed, mutations in THP cause a group of inherited kidney diseases, and altered THP expression is associated with increased risks of urinary tract infection, kidney stone, hypertension, hyperuricemia and acute and chronic kidney diseases. Despite the recent surge of information surrounding THP’s physiological functions and disease involvement, our knowledge remains incomplete regarding how THP is normally regulated by external and intrinsic factors, how precisely THP deficiency leads to urinary and systemic pathophysiology and in what clinical settings THP can be used as a theranostic biomarker and a target for modulation to improve patient outcomes.