Disease relevance of GNAI2

• Inhibiting Galpha subunit 2 protein, which is encoded by the GNAI2 gene, is suggested to be pathogenic for essential hypertension and/or insulin resistance [1].
• Overlapping homozygous 3p21.3 deletions in lung cancer cell lines involving GNAI2 were characterized and found to involve a region of genomic instability [2].
• We conclude that, in the familial IBD and colon cancer/dysplasia patients studied, there is no detectable mutation in the codon 179 of the GNAI2 gene [3].
• Absence of GNAI2 codon 179 oncogene mutations in inflammatory bowel disease [3].
• The pathogenesis of AIMBAD appears to be heterogeneous, as recent reports have demonstrated GIP-mediated hypercortisolism and familial AIMBAD [4].

High impact information on GNAI2

• These semaphorin genes are approximately 70 kb apart flanking two GTP-binding protein genes, GNAI-2 and GNAT-1 [5].
• GNAT1 and GNAI2 were found to map adjacent to each other on mouse chromosome 9 and GNAT2 was mapped on chromosome 17 [6].
• 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 [1].
• Seven single-nucleotide polymorphisms (SNP) at the GNAI2 locus were identified [1].
• One candidate, GIP #1, is significantly homologous (72% identity) to a chicken zinc finger protein, CTCF, which binds to insulator elements and thus attenuates enhancer cross-talk between physically adjacent promoters [7].

Chemical compound and disease context of GNAI2

• Following diet and weight-reduction there was a significant decrease in both fasting and post-prandial insulin levels in the obese subjects but there were no significant changes in glucose or GIP concentrations [8].

Biological context of GNAI2

• These mapping results are further supported by amplification of GNAI2-specific sequences in a monochromosomal human/rodent somatic cell hybrid containing only human chromosome 3 [9].
• Furthermore, the human GNAI2 gene is subject to point mutations at certain positions, including three at codon 179, all of which have been reported in human endocrine tumors [3].
• The complete sequence of Gnaz and the tandemly duplicated genes Gnai2 and Gnat1 were obtained from a Fugu genomic cosmid library [10].
• GIP not only enhances insulin secretion but also insulin gene expression and, therefore, it is a true insulinotropic hormone [11].
• A chimeric promoter-reporter gene construct linking the 5'-flanking region of the hGIP gene with the thymidine kinase gene of the herpes simplex virus was introduced into the genomes of mice by microinjection [12].

Anatomical context of GNAI2

• A cDNA for the human GNAI2 gene has been isolated from a human T-cell library and is mapped by chromosomal in situ hybridization to the short arm of chromosome 3 at 3p21 [9].
• A first granulocyte inhibitory protein (GIP I) responsible for the PMNL dysfunction in uraemia has been isolated and characterized [13].
• Originally characterized in terms of its gastric acid inhibitory properties, GIP (gastric inhibitory polypeptide) expressed in the upper small intestine, was subsequently shown to exert strong glucose-dependent insulin-releasing properties [11].
• Giant-cell interstitial Pneumonia (GIP) is a very uncommon respiratory disease [14].

Associations of GNAI2 with chemical compounds

• Compensation index, potentiation, and sensitivity to GIP were interrelated parameters (P < 0.05 or less). beta-Cell function parameters were also related to mean 24-h glucose levels (r2 = 0.63, P < 0.0001, multivariate model) [15].
• CONCLUSION: The close correlation between the use of pyrazinamide as measured by the GIP and NTR provides strong evidence that in the Netherlands tuberculosis is reported in conformity with the guidelines for notifiable diseases [16].
• The majority of cases of GIP are caused by exposure to cobalt, tungsten and other hard metals [14].

Other interactions of GNAI2

• Regional localization of the human G protein alpha i2 (GNAI2) gene: assignment to 3p21 and a related sequence (GNAI2L) to 12p12-p13 [9].
• Screening of the MEN 1 gene and genetic analysis of the hot spot regions of the GNAS 1 (codons 201 and 227) and GNAI 2 (codons 179 and 205) genes did not show any mutations in the constitutional DNA or the adrenal tissue DNA of the index patient [17].

Analytical, diagnostic and therapeutic context of GNAI2

• Fasting GIP concentrations were similar, but postprandial levels were significantly greater in the obese subjects during both the OGTT and MTT [8].

References