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Influence of genotype on urinary oxalate excretion

基因型对尿草酸盐排泄的影响

基本信息

批准号：
7277699
负责人：
CARLA G MONICO
金额：
$ 11.98万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-10 至 2008-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7277699
关键词：
Affect Age Alanine-glyoxylate aminotransferase Appendix Arts Attention Calcium Calcium Oxalate Calculi Caring Child Clinic Clinical Clinical Research Code Commit Defect Developed Countries Diagnosis Diagnostic Diet Dietary intake Disease Dose Elevation Enzymes Excretory function Extracorporeal Shockwave Lithotripsy Familiarity Family Fibrosis Foundations Functional disorder Gastrointestinal Diseases General Population Genes Genetic Polymorphism Genetic Transcription Genotype Glycolates Glyoxylates Hemorrhage Hepatic Hepatocyte High Pressure Liquid Chromatography Hydroxypyruvate reductase Hyperoxaluria Hypertension In Vitro Inborn Genetic Diseases Individual Inherited Injury Kidney Kidney Calculi Kidney Failure Knowledge Laboratories Lead Life London Medical center Mentors Metabolic Metabolic Pathway Metabolism Middle East Molecular Genetics Mutation Mutation Detection Nephrolithiasis Numbers Oral Outcome Oxalates Pathogenesis Patients Phenotype Physicians Population Predictive Factor Preventive Primary Hyperoxaluria Production Property Proteins Rate Recombinants Recurrence Reporting Research Proposals Residual state Risk Factors Role Scientist Severities Structure Subgroup Therapeutic Translations Universities Urine Variant Woman base clinical phenotype clinically relevant cohort college day design disorder risk enzyme activity enzyme deficiency experience follow-up glycolate glyoxylate insight men novel patient oriented peroxisome protein expression pyridoxine response urinary

项目摘要

DESCRIPTION (provided by applicant): The primary hyperoxalurias (PH) are inbom errors of glyoxylate metabolism characterized by excessive production and urinary excretion of oxalate, recurrent calcium oxalate nephrolithiasis and renal failure. A number of mutations have been described in the causative enzymes (alanine:glyoxylate aminotransferase or AGT in PHI, and glyoxylate:hydroxypyruvate reductase or GR/HPR in PHII) but clinically relevant correlations between genotype and phenotype are currently lacking. The Mayo Clinic serves as a tertiary referral center for PH and has decades of extensive diagnostic, therapeutic, and long-term clinical follow-up experience, with one of the largest PH patient cohorts followed at a single medical center in the world. Although PH is rare, idiopathic calcium oxalate nephrolithiasis is extremely common, and mild hyperoxaluria appears to be an important pathogenic factor in many affected patients. Therefore, increased understanding regarding the interaction of diet and metabolic pathways of oxalate production, e.g. the role of AGT, could lead to important insights regarding renal stone pathogenesis. The applicant has devoted the last 4 years to intensive study of the molecular genetics of hyperoxaluria, including 2 years as a Mayo Foundation Scholar at University College London (UCL). A committed group of clinical and research mentors, both at Mayo and UCL, has been established to facilitate successful completion of 3 Specific Aims that are designed to rigorously define the effect of specific mutations and polymorphisms on oxalate excretion and clinical phenotype in hyperoxaluric states. (1) Denaturing high-performance liquid chromatography will be employed to efficiently screen the well-characterised Mayo cohort of PH patients for described and novel mutations, as well as polymorphisms. (2) All newly-described mutations will be expressed to study their function in vitro and verify their disease-causing potential. (3) The effect of normal allelic variation at the AGT locus on urine oxalate excretion and pyridoxine responsiveness will be defined in a group of idiopathic calcium oxalate stone formers. The applicant's long-term objective is to establish an investigative state-of the- art laboratory devoted to the study of the molecular genetics of hyperoxaluria.

描述（由申请人提供）：

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Phenotypic and functional analysis of human SLC26A6 variants in patients with familial hyperoxaluria and calcium oxalate nephrolithiasis.

DOI：
10.1053/j.ajkd.2008.07.041
发表时间：
2008-12
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
0
作者：
Monico CG;Weinstein A;Jiang Z;Rohlinger AL;Cogal AG;Bjornson BB;Olson JB;Bergstralh EJ;Milliner DS;Aronson PS
通讯作者：
Aronson PS