Association of hGrb10 Genetic Variations With Type 2 Diabetes in Caucasian Subjects

Paola, Rosa Di; Ciociola, Ester; Boonyasrisawat, Watip; Nolan, D.; Duffy, Jill; Miscio, Giuseppe; Cisternino, Carmela; Fini, G.; Tassi, Vittorio; Doria, Alessandro; Trischitta, Vincenzo

doi:10.2337/diacare.2951181a

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…In a recent report by Di Paola et al (30), the A-allele of rs4947710, a synonymous coding SNP in Grb10, was associated with decreased risk of type 2 diabetes in a relatively homogeneous population of Italian Caucasians (P ϭ 0.0001). This SNP was not part of the 100K SNP panel nor was our most highly type 2 diabetes-associated SNP (rs2237457) genotyped in the Italian sample.…”

Section: ϫ5mentioning

confidence: 91%

Identification of Novel Candidate Genes for Type 2 Diabetes From a Genome-Wide Association Scan in the Old Order Amish

et al. 2007

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OBJECTIVE-We sought to identify type 2 diabetes susceptibility genes through a genome-wide association scan (GWAS) in the Amish.RESEARCH DESIGN AND METHODS-DNA from 124 type 2 diabetic case subjects and 295 control subjects with normal glucose tolerance were genotyped on the Affymetrix 100K single nucleotide polymorphism (SNP) array. A total of 82,485 SNPs were tested for association with type 2 diabetes. Type 2 diabetesassociated SNPs were further prioritized by the following: 1) associations with 5 oral glucose tolerance test (OGTT) traits in 427 nondiabetic Amish subjects, and 2) in silico replication from three independent 100L SNP GWASs (Framingham Heart Study Caucasians, Pima Indians, and Mexican Americans) and a 500K GWAS in Scandinavians. RESULTS-The strongest association (P ϭ 1.07 ϫ 10 Ϫ5 ) was for rs2237457, which is located in growth factor receptor-bound protein 10 (Grb10), an adaptor protein that regulate insulin receptor signaling. rs2237457 was also strongly associated with OGTT glucose area under the curve in nondiabetic subjects (P ϭ 0.001). Of the 1,093 SNPs associated with type 2 diabetes at P Ͻ 0.01, 67 SNPs demonstrated associations with at least one OGTT trait in nondiabetic individuals; 80 SNPs were nominally associated with type 2 diabetes in one of the three independent 100K GWASs, 3 SNPs (rs2540317 in MFSD9, rs10515353 on chromosome 5, and rs2242400 in BCAT1 were associated with type 2 diabetes in more than one population), and 11 SNPs were nominally associated with type 2 diabetes in Scandinavians.One type 2 diabetes-associated SNP (rs3845971, located in FHIT) showed replication with OGTT traits and also in another population. CONCLUSIONS-Our

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Section: ϫ5mentioning

confidence: 91%

Identification of Novel Candidate Genes for Type 2 Diabetes From a Genome-Wide Association Scan in the Old Order Amish

et al. 2007

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“…GRB10 acts as a negative regulator of signaling from the insulin receptor (11)(12)(13)(14)(15)(16). GRB10 was identified in genome-wide studies as a candidate gene for type 2 diabetes (17)(18)(19). GRB10 induced type 2 diabetes in a nonobese mouse model of diabetes (20) and was implicated in maternal imprinting and heritable effects on glucose tolerance (21)(22)(23)(24)(25).…”

mentioning

confidence: 99%

Carrageenan Inhibits Insulin Signaling through GRB10-mediated Decrease in Tyr(P)-IRS1 and through Inflammation-induced Increase in Ser(P)307-IRS1

Bhattacharyya

Feferman

Tobacman

2015

Journal of Biological Chemistry

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Background:The common food additive carrageenan inhibits insulin signaling by increasing Ser(P) 307 -IRS1, leading to reduced Ser(P) 473 -AKT. Results: Carrageenan also inhibits insulin signaling by increasing expression of GRB10, an inhibitor of Tyr(P)-IRS1. Conclusion: Combined effects of carrageenan on Tyr(P)-IRS1 and Ser(P) 307 -IRS1 completely block the insulin-induced increase in Ser(P) 473 -AKT. Significance: Carrageenan impairs glucose tolerance by inflammatory and transcriptional effects that lead to insulin resistance.

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“…As discussed below, single nucleotide polymorphisms (SNPs) at two of these loci (7q32 and 11p15) have been implicated in parent-of-origin-specific associations with T2DM [35]. Association of SNPs within GRB10 with T2DM have also been reported [36,37], although results have been conflicting [38], perhaps in part as a result of lack of examination of parent-of-origin effects.…”

Section: Q24-related Transient Neonatal Diabetes Mellitusmentioning

confidence: 99%

Genomic imprinting in diabetes

Mitchell

Pollin

2010

Genome Med

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Genomic imprinting refers to a class of transmissible genetic effects in which the expression of the phenotype in the offspring depends on the parental origin of the transmitted allele. The DNA from one parent may be epigenetically modified so that only a single allele of the imprinted gene is expressed in the offspring. Although imprinting has an important role in the regulation of growth and development through its role in regulating gene expression, its contribution to susceptibility to common complex disorders is not well understood. We summarize current views on the role of imprinting in diabetes and in particular chromosome 6q24-related transient neonatal diabetes mellitus, the best known example of an imprinted genetic disorder that leads to diabetes.

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Association of hGrb10 Genetic Variations With Type 2 Diabetes in Caucasian Subjects

Cited by 14 publications

References 24 publications

Identification of Novel Candidate Genes for Type 2 Diabetes From a Genome-Wide Association Scan in the Old Order Amish

Identification of Novel Candidate Genes for Type 2 Diabetes From a Genome-Wide Association Scan in the Old Order Amish

Carrageenan Inhibits Insulin Signaling through GRB10-mediated Decrease in Tyr(P)-IRS1 and through Inflammation-induced Increase in Ser(P)307-IRS1

Genomic imprinting in diabetes

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