Autoimmune Hepatitis: Genetic and Environmental Risks

自身免疫性肝炎：遗传和环境风险

• 批准号: 10445144
• 负责人: Craig S Lammert
• 金额: $ 6.91万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-29 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10445144
• 关键词: Active Learning; Acute; Address; Age; Age of Onset; Alleles; Autoimmune; Autoimmune Diseases; Autoimmune Hepatitis; Award; Biological; Biometry; Breast Feeding; Characteristics; Chromosome 6; Clinic; Clinical Research; Clinical Virology; Coffee; Communicable Diseases; Consumption; Control Groups; Data; Data Analyses; Development Plans; Disease; Drug Hypersensitivity; Enrollment; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiology; Ethnic Origin; Exposure to; Family member; Fibrosis; Funding; Future; Gender; Genetic; Genetic Determinism; Genetic Risk; Genetic Variation; Genetic study; Genomic DNA; Genomics; Genotype; Goals; HLA Antigens; Haplotypes; Hepatocyte; Hepatology; Heterogeneity; Histocompatibility Antigens Class I; Immune; Immunologics; Immunology; Individual; Infection; Infrastructure; Investigation; K-Series Research Career Programs; Knowledge; Link; Liver Dysfunction; Liver diseases; Mediating; Medical; Medical History; Mentors; Mentorship; Modeling; Molecular Epidemiology; Natural History; Newly Diagnosed; Outcome; Pathogenesis; Patients; Pharmaceutical Preparations; Phenotype; Physicians; Positioning Attribute; Prospective Studies; Prospective cohort; Race; Recording of previous events; Recurrence; Research; Research Personnel; Resolution; Risk; Risk Factors; Sampling; Senior Scientist; Serology test; Structure; Surveys; Testing; Tobacco use; Translational Research; Transplantation; Urinary tract infection; Viral; Virus Diseases; autoimmune pathogenesis; base; career; career development; clinical care; cohort; cost effective; deep sequencing; disease heterogeneity; disease phenotype; epidemiologic data; experience; gene environment interaction; genetic epidemiology; genetic risk factor; genetic variant; genomic epidemiology; human leukocyte antigen testing; liver injury; multidisciplinary; novel; outcome prediction; pleiotropism; programs; prospective; recruit; research and development; risk variant; skills; social media; tool; treatment response

PROJECT SUMMARY The principle genetic and environmental risk factors underlying the pathogenesis of autoimmune hepatitis (AIH) are not well investigated. Better understanding the explainable risks in AIH is essential to elucidate disease heterogeneity, predict outcomes, and transition to a model of individualized clinical care. In this career development application, the candidate is proposing a hypothesis-driven research strategy to address important knowledge gaps in the field of genetic and environmental risks in AIH. This builds on a recently completed prospective study of patients with AIH and matched controls funded by an institutional KL2 award. The specific aims of the research strategy are to (1) develop a large cohort of patients with AIH and matched controls with detailed assessment of environmental risk factors and linked biologic samples utilizing traditional and novel recruitment strategies; (2) interrogate selected environmental triggers associated with new onset AIH; and (3) identify novel disease specific HLA associations and assess for genetic and environmental interactions. To achieve these aims, the candidate will (1) develop a large cohort of patients with well phenotyped AIH and matched controls who undergo carefully assessment of environmental risk factors and provide their genomic DNA; (2) systematically interrogate viral and medication-related environmental triggers of newly diagnosed AIH patients and two control groups; (3) conduct HLA deep sequencing utilizing the Illumina MiSeq platform to identify putative HLA-specific associations and perform gene-environment interaction studies. The proposed career development plan integrates in-depth mentoring from a multidisciplinary team of senior scientists, advanced coursework in genomics, genetic and molecular epidemiology, and immunology; experiential learning through the conduct of the proposed research plan, and a highly supportive research environment. The mentorship team, which includes independent investigators with expertise in clinical and translational research in hepatology (Chalasani), immunologic-mediated drug-hypersensitivity and HLA genetics (Phillips), clinical virology and mentoring (Gupta); epidemiologic data analysis and biostatistics (Gao), will guide the candidate's research and career development. The superb institutional infrastructure for facilitating junior investigators and substantial institutional commitment to the candidate greatly strengthen this application. At the conclusion of this program, the candidate will be well positioned to become an independent physician-investigator in autoimmune liver diseases and hepatogenomics.!

项目总结

项目成果

Extrahepatic Autoimmune Diseases are Prevalent in Autoimmune Hepatitis Patients and Their First-Degree Relatives: Survey Study.

• DOI: 10.2196/ijmr.9625
• 发表时间: 2018-12-19
• 期刊: Interactive journal of medical research
• 影响因子: 2
• 作者: Fogel, Rachel;Comerford, Megan;Lammert, Craig
• 通讯作者: Lammert, Craig

Utilization and Impact of Complementary and Alternative Medicines in Symptomatic Autoimmune Hepatitis Patients.

• DOI: 10.1007/s10620-021-07112-0
• 发表时间: 2022-07
• 期刊: DIGESTIVE DISEASES AND SCIENCES
• 影响因子: 3.1
• 作者: Gelow, Kayla;Chalasani, Sai;Green, Kelsey;Lammert, Craig
• 通讯作者: Lammert, Craig

Genetic and Environmental Risk Factors for Autoimmune Hepatitis.

• DOI: 10.1002/cld.798
• 发表时间: 2019-07-01
• 期刊: Clinical liver disease
• 作者: Lammert, Craig

Environmental risk factors are associated with autoimmune hepatitis.

• DOI: 10.1111/liv.14944
• 发表时间: 2021-10
• 期刊: Liver international : official journal of the International Association for the Study of the Liver
• 作者: Lammert C;Chalasani SN;Atkinson EJ;McCauley BM;Lazaridis KN
• 通讯作者: Lazaridis KN

Autoimmune hepatitis and metabolic syndrome-associated disease development: a U.S. cohort study.

自身免疫性肝炎和代谢综合征相关疾病的发展：美国队列研究。

• DOI: 10.1111/apt.17191
• 发表时间: 2022
• 期刊: Alimentary pharmacology & therapeutics
• 影响因子: 7.6
• 作者: Jalal,MuhammadI;Brahmbhatt,Mihir;Green,Kelsey;Weinberg,EthanM;Lammert,Craig;Bittermann,Therese
• 通讯作者: Bittermann,Therese