Our results demonstrate a strong genetic heterogeneity among the ethnic group and suggest that the Gly40Ser mutation of the glucagon receptor gene plays little role, if any, in the pathogenesis of type 2 diabetes and essential hypertension in the Taiwanese population.
We have previously reported that a single heterozygous missense mutation in exon 2 of the glucagon receptor gene, which changes a glycine to a serine (Gly40Ser), is associated with NIDDM in a French population.
Although the frequency of the Gly40Ser polymorphism in NIDDM observed in France is not confirmed in our population, this genetic variance is also evident in Germany.
None of the Japanese diabetic patients showed Gly40Ser mutation and the association of this mutation with NIDDM was significantly different (p < 4.10(-5) vs French, p < 3.10(-6) vs Sardinian by Fisher's exact test).
Absence of association between the Gly40-->Ser mutation in the human glucagon receptor and Japanese patients with non-insulin-dependent diabetes mellitus or impaired glucose tolerance.
In conclusion, our results indicate that the Gly40Ser variation is not associated with NIDDM in the Sardinian population and that its frequency varies in different parts of Sardinia.
Taken together, the data do not support the suggested involvement of the Gly40Ser polymorphism in impaired glucose tolerance and the hypothesis of an association between NIDDM and the glucagon receptor gene in this population.
Recently, subtypes of typical NIDDM were suggested based on missense mutations of mitochondrial DNA [tRNALeu(UUR)] and the glucagon receptor gene (Gly40Ser).
Our results suggest that Gly40Ser polymorphism of the GCG-R gene is not associated with NIDDM in the Russian population and point to the genetic heterogeneity of NIDDM in different ethnic groups.
A total of 348 unrelated Japanese subjects (220 with NIDDM, 53 with impaired glucose tolerance (IGT) and 75 normal subjects) were screened for the presence of the Gly40-Ser mutation.
We conclude that the Gly40Ser polymorphism of the GCGR gene is associated with higher risk of hypertension and with enhanced proximal tubular sodium reabsorption, a factor possibly contributing to hypertension in this group.
The Gly40Ser polymorphism was not significantly associated with hypertension in the whole study population, although the frequency of 40Ser carriers in hypertensive subjects was double that in normotensive subjects (3.1% in hypertensives versus 1.5%; P=0.087).
Taken together, the data do not support the suggested involvement of the Gly40Ser polymorphism in impaired glucose tolerance and the hypothesis of an association between NIDDM and the glucagon receptor gene in this population.
1.Previous glucagon receptor gene (GCGR) studies have shown a Gly40Ser mutation to be more prevalent in essential hypertension and to affect glucagon binding affinity to its receptor.
Our results demonstrate a strong genetic heterogeneity among the ethnic group and suggest that the Gly40Ser mutation of the glucagon receptor gene plays little role, if any, in the pathogenesis of type 2 diabetes and essential hypertension in the Taiwanese population.
Absence of association between the Gly40-->Ser mutation in the human glucagon receptor and Japanese patients with non-insulin-dependent diabetes mellitus or impaired glucose tolerance.
Patients with diabetes and carriers of Gly40Ser showed basal C-peptide levels significantly lower than noncarriers (0.70 ng/mL versus 1.50 ng/mL, p = 0.008).