Hind III Site Causing Proinsulin Kyoto and Pst I Site Polymorphism of the Insulin Gene in Japanese: Its Lack of Association with Either IDDM or NIDDM.

Abstract

Abstract. The gene encoding Proinsulin Kyoto has been isolated and characterized by DNA sequencing, indicating that the molecular basis of the disorder is a G-T point mutation in the insulin gene which creates a Hind III site. In addition, in the 3'-untranslated region of the mutant insulin gene, a Pst I site negative, a type allele was found, and in the normal gene, a Pst I site positive, f3 type allele was found. In order to clarify the frequency of the mutation and to determine whether this mutation is associated with diabetes mellitus or not, we have investigated Hind III polymorphism in 91 normal Japanese subjects and patients with IDDM and NIDDM. No cases with the Proinsulin Kyoto gene were found among the subjects examined. Secondly, to determine whether this a type allele is associated with DM in Japanese, we investigated Pst I polymorphism in the same subjects. The frequencies of the a type and 13 type alleles were 92% and 8%, respectively. No significant difference in genotypic frequency was found among normal, NIDDM, and IDDM. We conclude that the Proinsulin Kyoto gene is not a common cause of DM and the occurrence of the a type insulin gene in Japanese diabetes is more frequent than in other races, so this Pst I polymorphism is not a marker for diabetes mellitus in Japanese. Key words: ProinsulinKyoto, NIDDM, Insulin gene, RFLP, Pst I site.(Endocrine journal 41: [71][72][73][74]1994) A NEW TYPE OF hyperproinsulinemia has recently been reported by our laboratory in a 65-yrold non-obese Japanese man who developed NIDDM [1]. A family study revealed that his son and daughter also showed signs of fasting hyperinsulinemia.Analysis of their sera by reverse phase high performance liquid chromatography demonstrated a minor peak of human insulin (5%) and a major peak of Proinsulin-like material (95%). Amplification and sequencing of the products of the insulin gene by polymerase chain reac-

Systematic Search for Single Nucleotide Polymorphisms in the Insulin Gene: Evidence for a High Frequency of −23T→A in Japanese Subjects

“…The allele frequency of the alpha allele, although haplotypes were not examined, is reported to be 92% in Japanese and 77% in southern Indian subjects (16,17). An alpha allele is also reported to be dominant in Korean (13).…”