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Several lines of evidence suggest a strong genetic component to NIDDM. To clarify the role of glucokinase gene in the development of NIDDM, restriction fragment length polymorphism (RFLP) of glucokinase gene and 3' microsatellite polymorphism analyses by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) were performed in NIDDM and control subjects. Compared to NIDDM with 1.3 kb allele/Pvu I digestion of glucokinase, 10% of NIDDM did not demonstrate 1.3 kb allele and these patients were characterized by increased insulin secretion. In 3' microsatellite polymorphism analysis, autoradiography of PCR products revealed three different alleles, including Z, Z + 2 and Z + 4. Z was the most common allele in both NIDDM and nondiabetic controls. There was no significant allele associated with NIDDM. Frequency of the homozygote Z/Z genotype was significantly lower in NIDDM subjects (16.7%) compared to normal control (46.7%)(p < 0.05). There was no difference in clinical findings according to 3' microsatellite genotypes in NIDDM. These data suggest that there does not appear to be a significant glucokinase allele associated with NIDDM but Z/Z genotype may play a suppressive role in the pathogenesis of a certain type of NIDDM in Korea. Further studies may be required to identify the molecular basis of this association.

Apolipoprotein E (apo E) plays a role in the regulation of the lipid metabolism of humans. Apo E, 229 amino acid polypeptide, is classified into three major isoform (E2, E3, E4) according to the differences of amino acid in position 112 and 158. In the normal population apo E3 isoform is most prevalent and apo E2 or E4 is frequently associated with hyperlipoproteinemia. To find out the frequency of apo E isoform distribution in the Korean population, apo E genotyping was performed. After amplification of apoE gene by polymerase chain reaction (PCR), restriction isotyping was done by cleavage with restriction enzyme Hha I and polyacrylamide gel electrophoresis. The apo E allele frequency in 73 normal subjects was 4.8% for E2, 84.9% for E3 and 10.3% for E4. In diabetic patient with hyperlipoproteinemia, the frequency of apo E allele was 6.3% for E2, 81.0% for E3 and 12.7% for E4. There was no significant difference in apo E isoform distribution between diabetics and normal populations. But in patients with cardiovascular disease with hyperlipidemia, the apo E4 allele frequency was significantly higher than normal (20.0% vs 10.3%, p < 0.005). Apo E3 was the most common isoform in normal and diabetic subjects and apo E2 isoform was rather low frequency compared to Caucasians. This pattern is similar to the Japanese population but somewhat different from other populations. From the data of a high association of apo E4 allele and cardiovascular disease with hypercholesterolemia, apo E isoform may be one of the determinants of hyperlipoproteinemia. The PCR method may be useful in apo E genotyping.