Dataset Information

The T allele of TCF7L2 rs7903146 is associated with decreased glucose tolerance after bed rest in healthy older adults.

ABSTRACT: Inpatient populations are at increased risk of hyperglycemia due to factors such as medications, physical inactivity and underlying illness, which increases morbidity and mortality. Unfortunately, clinicians have limited tools available to prospectively identify those at greatest risk. We evaluated the ability of 10 common genetic variants associated with development of type 2 diabetes to predict impaired glucose metabolism. Our research model was a simulated inpatient hospital stay (7 day bed rest protocol, standardized diet, and physical inactivity) in a cohort of healthy older adults (n = 31, 65 ± 8 years) with baseline fasting blood glucose < 100 mg/dL. Participants completed a standard 75 g oral glucose tolerance test (OGTT) at baseline and post-bed rest. Bed rest increased 2-h OGTT blood glucose and insulin independent of genetic variant. In multiple regression modeling, the transcription factor 7-like 2 (TCF7L2) rs7903146 T allele predicted increases in 2-h OGTT blood glucose (p = 0.039). We showed that the TCF7L2 rs7903146 T allele confers risk for loss of glucose tolerance in nondiabetic older adults following 7 days of bed rest.

SUBMITTER: Fry JL

PROVIDER: S-EPMC9046412 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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The T allele of TCF7L2 rs7903146 is associated with decreased glucose tolerance after bed rest in healthy older adults.

Fry Jean L JL Munson Brooke D BD Thompson Katherine L KL Fry Christopher S CS Paddon-Jones Douglas D Arentson-Lantz Emily J EJ

Scientific reports 20220427 1

Inpatient populations are at increased risk of hyperglycemia due to factors such as medications, physical inactivity and underlying illness, which increases morbidity and mortality. Unfortunately, clinicians have limited tools available to prospectively identify those at greatest risk. We evaluated the ability of 10 common genetic variants associated with development of type 2 diabetes to predict impaired glucose metabolism. Our research model was a simulated inpatient hospital stay (7 day bed r ...[more]

PMID: 35477971

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Project description:Hereditary Multiple Exostoses (HME) is an autosomal-dominant disorder characterized by benign cartilage tumors (exostoses) forming near the growth plates, leading to severe health problems. EXT1 and EXT2 are the two genes known to harbor heterozygous loss-of-function mutations that account for the vast majority of the primary genetic component of HME. However, patients present with wide clinical heterogeneity, suggesting that modifier genes play a role in determining severity. Our previous work has pointed to an imbalance of β-catenin signaling being involved in the pathogenesis of osteochondroma formation. TCF7L2 is one of the key 'gate-keeper' TCF family members for Wnt/β-catenin signaling pathway, and TCF7L2 and EXT2 are among the earliest associated loci reported in genome wide appraisals of type 2 diabetes (T2D). Thus we investigated if the key T allele of single nucleotide polymorphism (SNP) rs7903146 within the TCF7L2 locus, which is strongly over-represented among T2D cases, was also associated with HME. We leveraged genotype data available from ongoing GWAS efforts from genomics and orthopedic centers in the US, Canada and Italy. Collectively 213 cases and 1890 controls were analyzed and, surprisingly, the T allele was in fact significantly under-represented in the HME patient group [P = 0.009; odds ratio = 0.737 (95% C.I. 0.587-0.926)]; in addition, the direction of effect was consistent within each individual cohort. Immunohistochemical analyses revealed that TCF7L2 is differentially expressed and distributed in normal human growth plate zones, and exhibits substantial variability in human exostoses in terms of staining intensity and distribution. In summary, the data indicate that there is a putative genetic connection between TCF7L2 and EXT in the context of HME. Given this observation, we suggest that these loci could possibly modulate shared pathways, in particular with respect to β-catenin, and their respective variants interplay to influence HME pathogenesis as well as T2D.

Dataset Information

The T allele of TCF7L2 rs7903146 is associated with decreased glucose tolerance after bed rest in healthy older adults.

Publications

The T allele of TCF7L2 rs7903146 is associated with decreased glucose tolerance after bed rest in healthy older adults.

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