J Korean Diabetes Assoc.  1999 Oct;23(5):625-634.

Methylenetetrahydrofolate Reductase Polymorphism in Korean Type 2 Diabetic Patients with Macroangiopathy

• Oh KW
• Lee WY
• Ahn YB
• Song KH
• Yoo SJ
• Yoon KH
• Kang MI
• Cha BY
• Lee KW
• Son HY
• Kang SK

Abstract

BACKGROUND: Hyperhomocysteinemia is an inde-pendent risk factor for cardiovascular disease. Recently, a mutation (677CT) was identified in the methylenetetrahydrofolate reductase (MTHFR) gene, leading to the substitution of valine (V) for alanine (A). This mutation causes a reduced folate-dependent enzyme activity which leads to increased homocysteine. In this study, we examined the association between the V allele of the methylenetetrahydrofolate reductase gene and macroangiopathy in Korean patients with type 2 diabetes mellitus. METHODS: In 54 type 2 diabetic patients with macroangiopathy and 198 normal subjects, the MTHFR genotypes were analyzed by polymerase chain reaction (PCR), followed by Hinfl digestion. To confirm the detection of the MTHFR polymorphism by the PCR-restriction fragment length polymorphism (RFLP) analysis, DNA Sequencing was performed on the PCR products. RESULT: The allele frequency of the V mutation was slightly higher in the patients than in the normal subjects, but that was statistically not significant. The crude ORs and 95% CIs for the allele frequency of the V mutation were 1.16 (0.76~1.79). Genotype frequencies were 35.9% for AA, 48.4% for AV, and 15.7% for VV in the normal subjects. And they were 31.5% for AA, 50.0 % for AU, and 18.5 % for VV in the patients. The crude ORs and 95% CIs for the VV genotype were 1.22 (0.56~2.67). In multiple regressian model, the VV genotype was not associated with diabetic macroangiopathy.
CONCLUSION
Although, the frequencies of VV genotype in Korean normals (=16%) are higher than those of other thical populations (=12%), this mutation is not associated with macroangiopathy in type 2 diabetic patients. But, our sample size was too small and larger cohort studies will be needed to confirm the effect of MTHFR polymorphism on the development of macroangiopathy in diabetic patients.

Keyword

Diabetic macroangiopathy; Methylene-tetrahydrofolate reductase polymorphism; Hyperhomocysteinemia

MeSH Terms

Alanine
Alleles
Cardiovascular Diseases
Cohort Studies
Diabetes Mellitus, Type 2
Digestion
Gene Frequency
Genotype
Homocysteine
Humans
Hyperhomocysteinemia
Methylenetetrahydrofolate Reductase (NADPH2)*
Polymerase Chain Reaction
Risk Factors
Sample Size
Sequence Analysis, DNA
Valine
Alanine
Homocysteine
Methylenetetrahydrofolate Reductase (NADPH2)
Valine