Genetic contribution of the BAT2 gene microsatellite polymorphism to the age-at-onset of insulin-dependent diabetes mellitus

Hashimoto, M.; Nakamura, Nobutaka; Obayashi, Hiroshi; Kimura, Fumiaki; Moriwaki, Akira; Hasegawa, Goji; Shigeta, Hirofumi; Kitagawa, Yoshihiro; Nakano, Katsunori; Kondo, Makoto; Ohta, Masafumi; NISHIMURA, Motonobu

doi:10.1007/s004399900100

Cited by 8 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, although PRRC2A is expressed at low levels in other organs of adult mice, such as spleen and lung, and brain, PRRC2A may still play a role in special developmental stages or specific cells in these tissues, such as Pdgfrα- or NG2-positive cells in the embryonic brain 21 . Moreover, epidemiological studies reported that PRRC2A is associated with cancer 73 , 74 , neurological diseases 75 , autoimmune diseases 76 , diabetes 77 , and obesity 78 . Altogether, PRRC2A is widely involved in the regulation of various diseases and may be a potential clinical treatment target.…”

Section: Discussionmentioning

confidence: 99%

The m6A reader PRRC2A is essential for meiosis I completion during spermatogenesis

et al. 2023

View full text Add to dashboard Cite

N6-methyladenosine (m6A) and its reader proteins YTHDC1, YTHDC2, and YTHDF2 have been shown to exert essential functions during spermatogenesis. However, much remains unknown about m6A regulation mechanisms and the functions of specific readers during the meiotic cell cycle. Here, we show that the m6A reader Proline rich coiled-coil 2A (PRRC2A) is essential for male fertility. Germ cell-specific knockout of Prrc2a causes XY asynapsis and impaired meiotic sex chromosome inactivation in late-prophase spermatocytes. Moreover, PRRC2A-null spermatocytes exhibit delayed metaphase entry, chromosome misalignment, and spindle disorganization at metaphase I and are finally arrested at this stage. Sequencing data reveal that PRRC2A decreases the RNA abundance or improves the translation efficiency of targeting transcripts. Specifically, PRRC2A recognizes spermatogonia-specific transcripts and downregulates their RNA abundance to maintain the spermatocyte expression pattern during the meiosis prophase. For genes involved in meiotic cell division, PRRC2A improves the translation efficiency of their transcripts. Further, co-immunoprecipitation data show that PRRC2A interacts with several proteins regulating mRNA metabolism or translation (YBX1, YBX2, PABPC1, FXR1, and EIF4G3). Our study reveals post-transcriptional functions of PRRC2A and demonstrates its critical role in the completion of meiosis I in spermatogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

The m6A reader PRRC2A is essential for meiosis I completion during spermatogenesis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…It has been newly recognized as an m6A reader in controlling neural development via regulating the stability of the Olig2 mRNA ( 27 ). Several reports have shown that microsatellite repeats and missense polymorphisms in the PRRC2A gene conferred increased risk in various immune-related diseases, including type 1 diabetes, rheumatoid arthritis, coeliac disease, lupus nephritis ( 28 – 31 ). Masao et al.…”

Section: Discussionmentioning

confidence: 99%

“…Masao et al. first reported that BAT2 microsatellite alleles are associated with the age-at-onset of insulin-dependent diabetes mellitus ( 28 ). The type 1 Diabetes Genetics Consortium (T1DGC) study also detected seven missense SNPs in the BAT2 gene associated with type 1 diabetes ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes

et al. 2022

View full text Add to dashboard Cite

ObjectivesN6-methyladenosine (m6A) is essential in the regulation of the immune system, but the role that its single nucleotide polymorphisms (SNPs) play in the pathogenesis of type 1 diabetes (T1D) remains unknown. This study demonstrated the association between genetic variants in m6A regulators and T1D risk based on a case-control study in a Chinese population.MethodsThe tagging SNPs in m6A regulators were genotyped in 1005 autoantibody-positive patients with T1D and 1257 controls using the Illumina Human OmniZhongHua-8 platform. Islet-specific autoantibodies were examined by radioimmunoprecipitation in all the patients. The mixed-meal glucose tolerance test was performed on 355 newly diagnosed patients to evaluate their residual islet function. The functional annotations for the identified SNPs were performed in silico. Using 102 samples from a whole-genome expression microarray, key signaling pathways associated with m6A regulators in T1D were comprehendingly evaluated.ResultsUnder the additive model, we observed three tag SNPs in the noncoding region of the PRRC2A (rs2260051, rs3130623) and YTHDC2 (rs1862315) gene are associated with T1D risk. Although no association was found between these SNPs and islet function, patients carrying risk variants had a higher positive rate for ZnT8A, GADA, and IA-2A. Further analyses showed that rs2260051[T] was associated with increased expression of PRRC2A mRNA (P = 7.0E-13), and PRRC2A mRNA was significantly higher in peripheral blood mononuclear cell samples from patients with T1D compared to normal samples (P = 0.022). Enrichment analyses indicated that increased PRRC2A expression engages in the most significant hallmarks of cytokine-cytokine receptor interaction, cell adhesion and chemotaxis, and neurotransmitter regulation pathways. The potential role of increased PRRC2A in disrupting immune homeostasis is through the PI3K/AKT pathway and neuro-immune interactions.ConclusionThis study found intronic variants in PRRC2A and YTHDC2 associated with T1D risk in a Chinese Han population. PRRC2A rs2260051[T] may be implicated in unbalanced immune homeostasis by affecting the expression of PRRC2A mRNA. These findings enriched our understanding of m6A regulators and their intronic SNPs that underlie the pathogenesis of T1D.

show abstract

“…The PRRC2A gene is a TF whose biological function remains poorly understood, but it is important to point out that an SNP previously associated with BLV PVL development in cattle is located in the PRRC2A coding region of provoking a synonymous substitution (Carignano et al, 2018). Sequence-level polymorphisms linked to PRRC2A have been associated with susceptibility to different diseases in humans, such as susceptibility to rheumatoid arthritis (Singal et al, 2000), insulin-dependent diabetes mellitus (Hashimoto et al, 1999), or development of non-Hodgkin's lymphoma (Nieters et al, 2012). The expression of this gene seems to be higher in HPVL compared with LPVL animals (Figures 1 and 2) but not statistically significant (Figure 1; Table 4).…”

Section: Discussionmentioning

confidence: 99%

Expression-based analysis of genes related to single nucleotide polymorphism hits associated with bovine leukemia virus proviral load in Argentinean dairy cattle

Petersen

Carignano

Archilla

et al. 2021

Journal of Dairy Science

View full text Add to dashboard Cite

In dairy cattle infected with bovine leukemia virus (BLV), the proviral load (PVL) level is directly related to the viral transmission from infected animals to their healthy herdmates. Two contrasting phenotypic groups can be identified when assessing PVL in peripheral blood of infected cows. A large number of reports point to bovine genetic variants (single nucleotide polymorphisms) as one of the key determinants underlying PVL level. However, biological mechanisms driving BLV PVL profiles and infection progression in cattle have not yet been elucidated. In this study, we evaluated whether a set of candidate genes affecting BLV PVL level according to whole genome association studies are differentially expressed in peripheral blood mononuclear cells derived from phenotypically contrasting groups of BLV-infected cows. During a 10-mo-long sampling scheme, 129 Holstein cows were phenotyped measuring anti-BLV antibody levels, PVL quantification, and white blood cell subpopulation counts. Finally, the expression of 8 genes (BOLA-DRB3, PRRC2A, ABT1, TNF, BAG6, BOLA-A, LY6G5B, and IER3) located within the bovine major histocompatibility complex region harboring whole genome association SNP hits was evaluated in 2 phenotypic groups: high PVL (n = 7) and low PVL (n = 8). The log 2 initial fluorescence value (N 0 ) transformed mean expression values for the ABT1 transcription factor were statistically different in high-and low-PVL groups, showing a higher expres-sion of the ABT1 gene in low-PVL cows. The PRRC2A and IER3 genes had a significant positive (correlation coefficient = 0.61) and negative (correlation coefficient = −0.45) correlation with the lymphocyte counts, respectively. Additionally, the relationships between gene expression values and lymphocyte counts were modeled using linear regressions. Lymphocyte levels in infected cows were better explained (coefficient of determination = 0.56) when fitted a multiple linear regression model using both PRRC2A and IER3 expression values as independent variables. The present study showed evidence of differential gene expression between contrasting BLV infection phenotypes. These genes have not been previously related to BLV pathobiology. This valuable information represents a step forward in understanding the BLV biology and the immune response of naturally infected cows under a commercial milk production system. Efforts to elucidate biological mechanisms leading to BLV infection progression in cows are valuable for BLV control programs. Further studies integrating genotypic data, global transcriptome analysis, and BLV progression phenotypes are needed to better understand the BLV-host interaction.

show abstract

Genetic contribution of the BAT2 gene microsatellite polymorphism to the age-at-onset of insulin-dependent diabetes mellitus

Cited by 8 publications

References 0 publications

The m6A reader PRRC2A is essential for meiosis I completion during spermatogenesis

The m6A reader PRRC2A is essential for meiosis I completion during spermatogenesis

Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes

Expression-based analysis of genes related to single nucleotide polymorphism hits associated with bovine leukemia virus proviral load in Argentinean dairy cattle

Contact Info

Product

Resources

About