Ask about this productRelated genes to: MAT1A Blocking Peptide
- Gene:
- MAT1A NIH gene
- Name:
- methionine adenosyltransferase 1A
- Previous symbol:
- -
- Synonyms:
- MAT, SAMS, MATA1, SAMS1
- Chromosome:
- 10q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1997-07-01
- Date modifiied:
- 2016-10-05
Related products to: MAT1A Blocking Peptide
Related articles to: MAT1A Blocking Peptide
- Epidemiological studies have consistently shown that chronic kidney disease is associated with increased Alzheimer disease risk. However, the underlying genetic architecture connecting these two conditions remains largely unexplored beyond genome-wide correlation analyses. Here, we conducted the first comprehensive, multi-ancestry, large-scale genetic investigation to identify shared genetic components between kidney function and Alzheimer disease. We leveraged large-scale genome-wide association study summary statistics for estimated glomerular filtration rate (N≈1.5 million European, N≈145,000 African ancestry) and late-onset Alzheimer disease (N=63,926 and N=398,058 in two European cohorts; N=9,168 in African ancestry) corrected for competing risk bias. We deployed a novel analytical framework integrating linkage disequilibrium score regression and polygenic risk score analysis, local analysis of [co]variant association, conjunctional false discovery rate analysis with Bayesian colocalization and fine-mapping, and bidirectional cis-Mendelian randomization to identify vertical pleiotropy. Despite the absence of genome-wide genetic correlation (r ≈ 0, p > 0.1), local genetic analysis uncovered striking regional heterogeneity. Sixteen pleiotropic loci were identified in individuals of European ancestry (conjunctional false discovery rate < 0.05), including , , , and , alongside 15 loci with significant local genetic correlations. Fine-mapping revealed that most pleiotropic loci harbored distinct causal variants for kidney function and Alzheimer disease, indicating horizontal pleiotropy. An ε4-defining allele (rs429358) was the sole variant with shared causality across both traits. We identified vertical pleiotropy using cis-Mendelian randomization at the and loci, providing evidence that kidney function-related genetic variants can causally affect Alzheimer disease risk at specific genomic loci. In contrast, loci such as , , and demonstrated horizontal pleiotropy, reflecting shared upstream biological pathways rather than direct causal mediation. Notably, was the only pleiotropic locus shared between European and African ancestry groups, underscoring marked ancestry-specific genetic architectures with critical implications for risk prediction and therapeutic translation. Alzheimer disease and kidney function share genetic components at specific loci rather than genome-wide, with mixed directional effects and horizontal pleiotropy explaining the absent global correlation despite strong local signals. At a subset of loci, we identified directional effects linking kidney genetic determinants to Alzheimer disease risk using cis-Mendelian randomization, supporting a complex kidney-brain genetic axis. Most overlap reflects horizontal pleiotropy, with limited loci showing vertical pleiotropy. was the only shared locus across ancestries, underscoring ancestry-specific architectures with implications for risk prediction. The multi-scale approach used here also provides a methodological framework for dissecting complex disease relationships missed by traditional genome-wide analyses. - Source: PubMed
Publication date: 2026/04/06
Yang DiyaYang YiheRay Nicholas RLi MengxuanBenchek PenelopeCrawford Dana CO'Toole John FSedor John RReitz ChristianeLynn AudreyZhu XiaofengHaines Jonathan L Bush William S - Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) characterised by high prevalence, increasing incidence among younger individuals and poor prognosis. NASH pathophysiology is not completely understood, and at present, there are no viable pharmacological treatments for this condition in clinical practice. Gentiopicroside (GPS). Can alleviate NASH by reducing inflammatory responses, inhibiting oxidative stress and influencing blood lipid levels. - Source: PubMed
Publication date: 2026/01/06
Chen JiaxinZuo HuilingJiao YuhangZhao HuanhuanMa XuanXiao YahuiLi XiangqiongZhao WeiShi AnhuaChen Wenhui - Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity, mortality, and premature death worldwide. Its pathogenesis is complex and incompletely understood, with disrupted methionine metabolism as a key contributor. This pathway converts methionine into S-adenosylmethionine (SAM or SAMe), the principal methyl donor, a precursor of glutathione (GSH), and a critical regulator of hepatocellular function. Alterations in methionine metabolism are primarily driven by downregulation of methionine adenosyltransferase 1A (), the liver-specific gene encoding the MATα1 subunit responsible for SAMe biosynthesis. Reduced expression and activity lead to hepatic SAMe and GSH deficiency, resulting in global hypomethylation, mitochondrial dysfunction, impaired lipid metabolism, and progressive liver injury, hallmarks of ALD. Recent studies show that MATα1 also localizes to hepatocyte mitochondria, where its selective depletion contributes to mitochondrial dysfunction in ALD. Experimental models demonstrate that SAMe supplementation restores methylation capacity, replenishes GSH, reduces oxidative stress, and improves mitochondrial function and liver histology. Preservation of mitochondrial MATα1 also protects against ALD, underscoring its importance in hepatocellular health. Clinical exploration of SAMe in early-stage ALD suggests potential benefit and motivates continued investigation into treatment strategies that build on and extend beyond supplementation. This review summarizes current knowledge on the role of the /SAMe axis in ALD pathophysiology, emphasizing molecular functions and critically evaluating preclinical and clinical evidence for potential therapy. - Source: PubMed
Publication date: 2025/12/11
Barbier-Torres LucíaChhimwal JyotiMato José MLu Shelly C - Succinylation, a recently characterized post-translational modification (PTM), is a ubiquitously occurring protein modification implicated in diverse biological processes via regulation of protein function and gene expression. CTBP1 encodes C-terminal binding proteins and generates multiple splice variants. However, the functional significance of CTBP1 succinylation in hepatocellular carcinoma (HCC) remains unexplored. - Source: PubMed
Qiu ZhengcaiWang QipengLi ShangshangLu GuangHan Jing - Colorectal liver metastasis (CRLM) occurs frequently in patients with colorectal cancer (CRC). Methionine adenosyltransferase (MAT) catalyzes the formation of S-adenosylmethionine, the principal methyl donor. MAT1A (encodes MATα1) is expressed mainly in normal adult liver, whereas MAT2A (encodes MATα2) is expressed in all extrahepatic tissues. MAT1A is a major defense against CRLM as loss of Mat1a sensitizes the liver to CRLM. In contrast, MAT2A is overexpressed in CRC and promotes oncogenicity. Here, we sought to determine if CRCs secrete MATα2 and if this influences CRLM. - Source: PubMed
Publication date: 2025/12/02
Justo MonicaLim YoungyiYang HepingFloris AndreaChandla SwatiDagar ManishaGangi AlexandraPosadas EdwinEdderkaoui MouadPandol StephenBhowmick NeilTomasi Maria LaudaLu Shelly C