Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4 Suppl 2
pubmed:dateCreated
2006-3-27
pubmed:abstractText
Inhibiting Galpha subunit 2 protein, which is encoded by the GNAI2 gene, is suggested to be pathogenic for essential hypertension and/or insulin resistance. The aim of this study was to determine whether GNAI2 variations modulate the risk for these abnormalities. Seven single-nucleotide polymorphisms (SNP) at the GNAI2 locus were identified. Because of either low allelic frequency or unlikely biologic relevance (i.e., synonymous or intronic), six SNP were not studied further. The -318C>G SNP (allelic frequency 6%) in the promoter region was studied for association with adiposity, systolic BP (SBP) and diastolic BP, fasting insulin and glucose, and lipids levels in 655 nondiabetic Caucasians from Italy. As compared with individuals who carry the C/C genotype, G carriers (i.e., individuals who carry either the G/G or the C/G genotype) had higher SBP (117.8 +/- 16 versus 113.6 +/- 12.6 mmHg; P = 0.010) and were at increased risk for hypertension (odds ratio 2.2; 95% confidence interval 1.1 to 4.5). Compared with the C, the G allele had 2.5-fold reduced transcriptional activity in transfected HEK293 cells. As predicted by the TRANSFAC database, competition with YY1 or Sp1 transcription factors specifically reduced the binding of HeLa cell nuclear proteins to -318C or -318G allele, respectively, as indicated by shifted electrophoretic mobility. A "supershift" of the nuclear proteins/-318G allele complex was observed after anti-Sp1 was added but not anti-YY1 antibody. The GNAI2 -318 C>G SNP impairs transcriptional activity through specific binding of Sp1 and is associated with high SBP in Caucasians from Italy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S115-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16565233-Adult, pubmed-meshheading:16565233-Alleles, pubmed-meshheading:16565233-Cell Line, pubmed-meshheading:16565233-Female, pubmed-meshheading:16565233-GTP-Binding Protein alpha Subunit, Gi2, pubmed-meshheading:16565233-Genetic Variation, pubmed-meshheading:16565233-HeLa Cells, pubmed-meshheading:16565233-Humans, pubmed-meshheading:16565233-Hypertension, pubmed-meshheading:16565233-Insulin Resistance, pubmed-meshheading:16565233-Italy, pubmed-meshheading:16565233-Male, pubmed-meshheading:16565233-Middle Aged, pubmed-meshheading:16565233-Polymorphism, Single Nucleotide, pubmed-meshheading:16565233-Promoter Regions, Genetic, pubmed-meshheading:16565233-Risk, pubmed-meshheading:16565233-Sp1 Transcription Factor, pubmed-meshheading:16565233-Transcription, Genetic, pubmed-meshheading:16565233-Transfection
pubmed:year
2006
pubmed:articleTitle
The -318 C>G single-nucleotide polymorphism in GNAI2 gene promoter region impairs transcriptional activity through specific binding of Sp1 transcription factor and is associated with high blood pressure in Caucasians from Italy.
pubmed:affiliation
Unit of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't