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Relationships between angiotensin I converting enzyme gene polymorphism and renal complications in Korean IDDM patients.

Oh TG, Shin CS, Park KS, Kim SY, Cho BY, Lee HK, Koh CS - Korean J. Intern. Med. (1996)

Bottom Line: 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.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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.

ABSTRACT

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 > 5 yrs) 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.

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Examples of the 3 patterns of the ACE insertion/deletion polymrphism. Homozygotes (II) have a band of 560 pb, homozygotes (DD) have a band of 270 pb and heterozygotes (ID) have both bands. The last lane shows size marker (Hae III).
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f1-kjim-11-2-133-6: Examples of the 3 patterns of the ACE insertion/deletion polymrphism. Homozygotes (II) have a band of 560 pb, homozygotes (DD) have a band of 270 pb and heterozygotes (ID) have both bands. The last lane shows size marker (Hae III).

Mentions: The insertion/large allele (560 bp) is designated I, and the deletion/shorter allele (270 bp) is designated D. Thus, each DNA sample yielded one of three possible genotypes represented as II, ID, and DD (Fig. 1). Frequencies for II, ID and DD genotypes were 23, 19 and 17 in IDDM patients, and 49, 41 and 17 in control subjects, respectively. Derived allele frequencies for I and D alleles were 55.1% and 44.9% in IDDM patients and 64.9% and 35.1% in control subjects, respectively, indicating that there was no significant difference between the two groups (Table 1). In IDDM patients, the subjects with proliferative diabetic retinopathy (PDR) were 11 patients. Frequencies for genotypes of ACE gene were 3, 4 and 4 in subjects with PDR and 20, 15, 13 in subjects without PDR, and derived allele frequencies for I and D alleles were 45.5% and 54.5% in subjects without PDR and 57.3% and 42.7% in subjects without PDR. There was no significant difference between subjects with or without PDR (Table 2).


Relationships between angiotensin I converting enzyme gene polymorphism and renal complications in Korean IDDM patients.

Oh TG, Shin CS, Park KS, Kim SY, Cho BY, Lee HK, Koh CS - Korean J. Intern. Med. (1996)

Examples of the 3 patterns of the ACE insertion/deletion polymrphism. Homozygotes (II) have a band of 560 pb, homozygotes (DD) have a band of 270 pb and heterozygotes (ID) have both bands. The last lane shows size marker (Hae III).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4532010&req=5

f1-kjim-11-2-133-6: Examples of the 3 patterns of the ACE insertion/deletion polymrphism. Homozygotes (II) have a band of 560 pb, homozygotes (DD) have a band of 270 pb and heterozygotes (ID) have both bands. The last lane shows size marker (Hae III).
Mentions: The insertion/large allele (560 bp) is designated I, and the deletion/shorter allele (270 bp) is designated D. Thus, each DNA sample yielded one of three possible genotypes represented as II, ID, and DD (Fig. 1). Frequencies for II, ID and DD genotypes were 23, 19 and 17 in IDDM patients, and 49, 41 and 17 in control subjects, respectively. Derived allele frequencies for I and D alleles were 55.1% and 44.9% in IDDM patients and 64.9% and 35.1% in control subjects, respectively, indicating that there was no significant difference between the two groups (Table 1). In IDDM patients, the subjects with proliferative diabetic retinopathy (PDR) were 11 patients. Frequencies for genotypes of ACE gene were 3, 4 and 4 in subjects with PDR and 20, 15, 13 in subjects without PDR, and derived allele frequencies for I and D alleles were 45.5% and 54.5% in subjects without PDR and 57.3% and 42.7% in subjects without PDR. There was no significant difference between subjects with or without PDR (Table 2).

Bottom Line: 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.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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.

ABSTRACT

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 > 5 yrs) 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.

Show MeSH
Related in: MedlinePlus