Polymorphism of the Human Ca²⁺-Sensing Receptor Gene in Japanese Individuals: No Relation to Non-Insulin Dependent Diabetes Mellitus

Abstract

A missense mutation in the Ca(2+)-sensing receptor (CaSR) gene was previously identified in a Japanese family with familial hypocalciuric hypercalcemia. Five members of this family with the mutation in the CaSR gene also showed abnormal glucose tolerance, whereas family members homozygous for the wildtype CaSR gene were normal in this respect. The potential relation between mutations in the CaSR gene and the incidence of diabetes mellitus was therefore investigated in 27 non-insulin dependent diabetic and 40 normal Japanese subjects. Each exon of the CaSR gene was amplified by the polymerase chain reaction and subjected to single-strand conformation polymorphism (SSCP) analysis. The region of the gene containing the sixth exon showed three distinct patterns on SSCP analysis in both diabetic patients and normal subjects. Direct sequencing of DNA revealed a T/C polymorphism in the fifth intron. The TT genotype was apparent in 59.3% of diabetic patients and in 45.0% of normal subjects. The CC genotype was present in 25.9% of diabetics and in 22.5% of normal subjects. The diabetic patients were divided into three groups on the basis of genotype for the polymorphism (TT, TC, or CC). However, there was no significant difference among the three groups with regard to the method of therapy, the incidence or severity of diabetic complications, duration or family history of disease, HbA1c level, or laboratory data. The polymorphism in the fifth intron of the CaSR gene does not therefore appear to be associated with non-insulin dependent diabetes mellitus.

A Patient with Type 2 Diabetes Mellitus Associated with Mutations in Calcium Sensing Receptor Gene and Mitochondrial DNA

“…However, we could not observe a significant association between mutations of CaSR gene and type 2 diabetes mellitus (26). So, we concluded that the mutations of CaSR gene may not be direct a determinant for the development of diabetes mellitus or IGT in this family.…”

The calcium-sensing receptor and related diseases

“…Six polymorphisms were found in the CASR gene: one (105) and, when analyzed in a large group of normal and affected individuals, no correlation was found between this mutation and the incidence of parathyroid adenoma or diabetes (106). The A/T 826 mutation was initially found in 4 parathyroid adenomas (107).…”

Association between calcium-sensing receptor gene polymorphisms and recurrent calcium kidney stone disease: A comprehensive gene analysis

“…The first exon of CASR could not be translated to protein. There is a large body of evidence now defining genotypic variation and its relation to phenotype and ethnic distribution of CASR, and for the association of its polymorphisms with some diseases such as hypertension [11], cancer [12,13] and diabetes [14,15]; however, with respect to urinary stone disease directly related with calcium homeostasis, more work is required. The incidence of urolithiasis is relatively high in Iran [16,17].…”