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  1. Effect of gasotransmitters treatment on expression of hypertension, vascular and cardiac remodeling and hypertensive nephropathy genes in left ventricular hypertrophy
    Ahmad A, Riaz Z, Sattar MA, Khan SA, John EJ, Rashid S, et al.
    Gene, 2020 May 05;737:144479.
    PMID: 32068124 DOI: 10.1016/j.gene.2020.144479
    BACKGROUND: Cardiac and renal dysfunction are often co-morbid pathologies leading to worsening prognosis resulting in difficulty in therapy of left ventricular hypertrophy (LVH). The aim of the current study was to determine the changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and upon treatment with gasotransmitter including H2S (hydrogen sulphide), NO (nitric oxide) and combined (H2S + NO).

    METHODS: A total of 72 Wistar Kyoto rats (with equivalent male and female animals) were recruited in the present study where LVH rat models were treated with H2S and NO individually as well as with both combined. Cardiac and renal physical indices were recorded and relative gene expression were quantified.

    RESULTS: Both cardiac and renal physical indices were significantly modified with individual as well as combined H2S + NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNFα and IGF1, mRNAs to be significantly higher (P ≤ 0.05) in the myocardia and renal tissues of LVH rats, while individual and combined H2S + NO treatment resulted in lowering the gene expression to normal/near to normal levels. The cardiac remodeling genes MYH7, TGFβ, SMAD4 and BRG1 expression were significantly up-regulated (P ≤ 0.05) in the myocardia of LVH where the combined H2S + NO treatment resulted in normal/near to normal expression more effectively as compared to individual treatments. In addition individual as well as combined H2S and NO treatment significantly decreased PKD1 expression in renal tissue, which was up-regulated in LVH rats (P ≤ 0.05).

    CONCLUSIONS: The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment of LVH rat model indicates important therapeutic potential of combined treatment with H2S + NO gasotransmitters in hypertension and cardiac hypertrophy when present as co-morbidity with renal complications.

  2. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma
    Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al.
    Nat Genet, 2016 May;48(5):556-62.
    PMID: 27064256 DOI: 10.1038/ng.3540
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.
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