Variant of Transcription Factor 7-Like 2 (TCF7L2) Gene and the Riskof Type 2 Diabetes

The specific gene that link to inheritance of type 2 diabetes that have
been identified thus far a not many. The following study is based on 2
long time large populations of health professionals. The particular
gene variant identified is found in people of European extract.

"Emerging evidence indicates that variation in the transcription factor
7-like 2 (TCF7L2) gene may play a role in the pathogenesis of type 2
diabetes. In a prospective, nested, case-control study (n = 3,520)
within the Nurses’ Health Study (687 type 2 diabetic case and 1,051
control subjects) and the Health Professionals Follow-up Study (886 case
and 896 control subjects), we examined the association of a common
variant of the TCF7L2 gene (rs12255372 [T/G]) with type 2 diabetes risk
among Caucasians. Frequencies of the T-allele were significantly higher
among case than control subjects; each copy of the T-allele was
associated with a 1.32-fold and 1.53-fold increased type 2 diabetes risk
in women and men, respectively. The odds ratios (95% CI) associated with
homozygous carriers of the T-allele were 1.86 (1.30–2.67) and 2.15
(1.48–3.13) in women and men, respectively. Population-attributable
risks for diabetes associated with the T-allele were 14.8 and 22.3% for
women and men, respectively. In a meta-analysis of 3,347 case and 3,947
control sujects, each copy of the T-allele was associated with a
1.48-fold increased risk. Our findings confirm that the TCF7L2 gene
represents an important locus for predicting inherited susceptibility to
type 2 diabetes.

.... The exact mechanism by which the TCF7L2 gene may be related to the
risk of type 2 diabetes has yet to be determined. Several lines of
evidence indicate that it could be through regulating glucagon-like
peptide 1 (GLP-1) by its roles in the Wnt signaling pathway. Human
T-cell transcription factor 4 (TCF-4), the TCF7L2 gene product, is a
high-mobility transcription factor that plays a pivotal role in the Wnt
signaling pathway, which is one of the key developmental and growth
regulatory mechanisms of the cell (7,21). TCF-4 regulates the
transcription of proglucagon gene in enteroendocrine cells, the gene
encoding the insulinotropic hormone GLP-1 in vitro (8).
Dominant-negative TCF-4 was shown to repress proglucagon gene mRNA
expression and GLP-1 synthesis (8). GLP-1 has been demonstrated to exert
critical effects on blood glucose homeostasis; GLP-1 can lower blood
glucose levels through the stimulation of insulin secretion and
biosynthesis, the inhibition of glucagon release and gastric emptying
and the enhancement of peripheral insulin sensitivity (8)." Source:
Variant of Transcription Factor 7-Like 2 (TCF7L2) Gene and the Risk of
Type 2 Diabetes in Large Cohorts of U.S. Women and Men -
http://diabetes.diabetesjournals.org...full/55/9/2645

Frank