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Sökning: WFRF:(Chakravarti A)

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33.
  • Terao, C, et al. (författare)
  • Recent Advances in Defining the Genetic Basis of Rheumatoid Arthritis
  • 2016
  • Ingår i: Annual review of genomics and human genetics. - : Annual Reviews. - 1545-293X .- 1527-8204. ; 17, s. 273-301
  • Tidskriftsartikel (refereegranskat)abstract
    • Rheumatoid arthritis (RA) is the most common inflammatory arthritis and exhibits genetic overlap with other autoimmune and inflammatory disorders. Although predominant associations with the HLA-DRB1 locus have been known for decades, recent data have revealed additional insight into the likely causative variants within HLA-DRB1 as well as within other HLA loci that contribute to disease risk. In addition, more than 100 common variants in non-HLA loci have been implicated in disease susceptibility. Genetic factors are involved not only in the development of RA, but also with various disease subphenotypes, including production and circulating levels of autoantibodies and joint destruction. The major current challenge is to integrate these new data into a precise understanding of disease pathogenesis, including the critical cell types and molecular networks involved as well as interactions with environmental factors. We predict that delineating the functional effects of genetic variants is likely to drive new diagnostic and therapeutic approaches to the disease.
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34.
  • Wen, Gen, et al. (författare)
  • An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension
  • 2007
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 16:14, s. 1752-1764
  • Tidskriftsartikel (refereegranskat)abstract
    • Granins regulate secretory vesicle formation in neuroendocrine cells and granin-derived peptides are co-released with neurotransmitters as modulatory signals at sympathetic sites. We report evidence for association between a regulatory polymorphism in Secretogranin II (SCG2) and hypertension in African-American subjects. The minor allele is ancestral in the human lineage and is associated with disease risk in two case-control studies and with elevated blood pressure in a separate familial study. Mechanistically, the ancestral allele acts as a transcriptional enhancer in cells that express endogenous Scg2, whereas the derived allele does not. ARIX (PHOX2A) and PHOX2B are identified as potential transactivating factors by oligonucleotide affinity chromatography and mass spectrometry and confirmed by chromatin immunoprecipitation. Each of these transcription factors preferentially binds the risk allele, both in vitro and in vivo. Population genetic considerations suggest positive selection of the protective allele within the human lineage. These results identify a common regulatory variation in SCG2 and implicate granin gene expression in the control of human blood pressure and susceptibility to hypertension.
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