Aldosterone synthase (CYP11B2) -344T/C polymorphism is not associated with the initiation and progression of diabetic nephropathy in Caucasian Type 1 diabetic patients.
OBJECTIVE
Aldosterone is one of the main effectors of the renin-angiotensin-aldosterone system regulating blood pressure. Previous studies have shown that the aldosterone synthase promoter polymorphism -344T/C influences aldosterone levels and is associated with hypertension, a risk factor for the initiation and progression of diabetic nephropathy. Therefore, we investigated whether the -344T/C polymorphism is associated with the development and progression of diabetic nephropathy in Type 1 diabetes mellitus.


METHODS
The -344T/C polymorphism was determined using standard PCR techniques in 422 Type 1 diabetic patients with overt diabetic nephropathy [mean age 43 years (SD 11)], and in 479 patients with persistent normoalbuminuria and long-standing Type 1 diabetes [age 47 years (SD 12), duration of diabetes 27 years (SD 10)]. Furthermore, we genotyped 163 Type 1 diabetic patients with overt diabetic nephropathy treated with angiotensis-converting enzyme inhibitors (ACE-I). These patients were followed for a median of 6 years (range 3-14), with nine measurements (range 3-29) of glomerular filtration rate (GFR), and had a decline in GFR of 3.1 (-3.2; 23.7) ml/min per year.


RESULTS
There was no significant difference between cases and controls in either genotype distributions (cases TT 0.33, TC 0.48, CC 0.19; controls TT 0.32, TC 0.48, CC 0.20) or allele frequencies (cases T/C 0.57/0.43; controls T/C 0.56/0.44). Furthermore, a genotype-phenotype interaction analysis in the normoalbuminuric patients revealed no differences in sex distribution, age, duration of diabetes, blood pressure, HbA(1c,) or urinary albumin excretion rate across genotypes. In the observational follow-up study, the rate of decline in GFR did not differ between groups of patients with different -344T/C genotype (P = 0.41). However, the T-allele made a statistically significant contribution to both systolic and diastolic pressure during follow-up (P = 0.006 and 0.032, respectively).


CONCLUSIONS
The -344T/C polymorphism of the aldosterone synthase gene is not associated with initiation or progression of diabetic nephropathy in Caucasian Type 1 diabetic patients, but modulates blood pressure variation.
Lajer
M
M
Steno Diabetes Center, Gentofte, Denmark. mlaj@steno.dk
Schjoedt
K J
KJ
Jacobsen
P
P
Tarnow
L
L
Parving
H-H
HH
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018709:Statistics, Nonparametric; D044465:White People
D000806:Angiotensin-Converting Enzyme Inhibitors; D019405:Cytochrome P-450 CYP11B2