Relationships between Angiotensin I Converting Enzyme Gene Polymorphism and Renal Complications in Korean IDDM Patients(*)

OBJECTIVES: The prognosis of IDDM is mainly dependent on complicated diabetic nephropathy which is probably determined by both metabolic abnormalities and genetic predisposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angiotensin II formation and kinins metabolism. The insertion(I)/deletion(D) polymorphism in intron 16 of ACE gene is strongly associated with ACE levels, and subjects homozygote for deletion (genotype DD) have the highest plasma values. Recently, it was reported that I/D polymorphism of ACE gene is associated with diabetic nephropathy in Caucasian IDDM patients. We studied the relationship between the ACE gene polymorphism and diabetic nephropathy in Korean IDDM patients. METHODS: The study population consisted of 59 IDDM patients (duration> 5yrs) and 107 control subjects. IDDM subjects were divided into 2 groups according to the presence or absence of diabetic nephropathy (with nephropathy: n=31, without nephropathy: n=28). After extraction of genomic DNA from peripheral blood leukocytes, PCR was performed using the sense primer (5′-GCC CTG CAG GTG TCT GCA GC-3′) and anti-sense primer (3′-TGC CCA TAA CAG TGC TTC ATA-5′), respectively. The PCR products were electrophoresed in 2% agarose gels, and DNA was visualized directly with ethidium bromide staining. RESULTS: Frequencies for II, ID and DD genotypes were similar in IDDM subjects and controls (23:19:17 vs 49:41:17, p=0.142) and derived allele frequencies for I and D alleles were similar in both groups (0.551:0.449 vs 0.649:0.351, p=0.098). The ACE genotype distributions were not different in diabetic subjects with or without nephropathy (12:9:10 vs 11:10:7, p=0.78) and derived allele frequencies were also similar (0.532:0.468 vs 0.571:0.429, p=0.81). CONCLUSION: The I and D allele frequency in our controls was different compared to ACE allele frequencies of Caucasian populations, but very similar compared to those of Chinese or Japanese subjects. We found that I/D polymorphism of ACE gene is not implicated in the diabetic nephropathy of Korean IDDM patients and may be explained by ethnic differences.