RGD Reference Report - Genetic Variants of TCF7L2 are Associated with Insulin Resistance and Related Metabolic Phenotypes in Taiwanese Adolescents and Caucasian Young Adults. - Rat Genome Database

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Genetic Variants of TCF7L2 are Associated with Insulin Resistance and Related Metabolic Phenotypes in Taiwanese Adolescents and Caucasian Young Adults.

Authors: Liu, PH  Chang, YC  Jiang, YD  Chen, WJ  Chang, TJ  Kuo, SS  Lee, KC  Hsiao, PC  Chiu, KC  Chuang, LM 
Citation: Liu PH, etal., J Clin Endocrinol Metab. 2009 Jun 9.
RGD ID: 2312433
Pubmed: PMID:19509102   (View Abstract at PubMed)
DOI: DOI:10.1210/jc.2009-0609   (Journal Full-text)

Objectives: The effect of TCF7L2 rs7903146 on glucose homeostasis is considered primarily due to impaired insulin secretion in European. As we previously demonstrated that TCF7L2 rs290487 near the 3' end of TCF7L2 was significantly associated with T2D in Taiwanese, we aimed to investigate potential mechanisms underlying the associations of rs290487 with T2D. Methods: Eighteen SNPs were tested for association with glucose/insulin homeostasis as well as other quantitative metabolic phenotypes using the quantitative transmission disequilibrium test (QTDT) in 525 Taiwanese adolescent twin-pairs and siblings. The results were further replicated in 116 non-diabetic normotensive Caucasian young adults. Results: Among the 18 SNPs, rs290487 C allele was significantly associated with higher 60, 90, and 120-min glucose concentrations (p= 0.001, 0.01, and 0.02, respectively), higher 60 and 90-min insulin concentrations (p= 0.01 and 0.01, respectively), and a lower insulin sensitivity index (p= 0.04). No association was found for rs290487 with measures of insulin secretion. The rs290487 C allele was also associated with HOMA-IR (p= 0.005) and insulin sensitivity index (p= 0.01) in Caucasian young adults. Another SNP rs10749127 C allele located in intron 4 was also associated features of the metabolic syndrome including elevated systolic (p= 0.02) and diastolic (p= 2.0x10(-4)) blood pressure, triglycerides (p= 7.0x10(-4)), and uric acid (p= 0.03). In a meta-analysis, the rs290487 C allele was confirmed to be associated with an increased risk of T2D (OR = 1.11, 95% CI 1.03-1.19, p=0.005) across East Asian populations. Conclusions: These findings support an important role for T2D risk-conferring gene TCF7L2 in insulin resistance in both Taiwanese and Caucasian youth, and underscore the emerging role of Wnt signaling in insulin resistance.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Insulin Resistance  IAGP 2312433DNA:SNP (human)RGD 
Insulin Resistance  ISOTCF7L2 (Homo sapiens)2312433; 2312433DNA:SNP (human)RGD 
type 2 diabetes mellitus  IAGP 2312433DNA:SNP (human)RGD 
type 2 diabetes mellitus  ISOTCF7L2 (Homo sapiens)2312433; 2312433DNA:SNP (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tcf7l2  (transcription factor 7 like 2)

Genes (Mus musculus)
Tcf7l2  (transcription factor 7 like 2, T cell specific, HMG box)

Genes (Homo sapiens)
TCF7L2  (transcription factor 7 like 2)


Additional Information