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Aldosterone synthase (CYP11B2)-344T/C polymorphism and renoprotective response to losartan treatment in diabetic nephropathy.
Scand J Clin Lab Invest. 2006; 66(3):173-80.SJ

Abstract

OBJECTIVE

It has been suggested that an aldosterone synthase gene polymorphism (CYP11B2 -344T/C) is predictive of the blood pressure lowering effect of angiotensin II receptor blockers in essential hypertension. We investigated whether this polymorphism is predictive of reductions in blood pressure and albuminuria and preservation of glomerular filtration rate (GFR) during short-term and long-term treatment with losartan in 57 hypertensive type-1 diabetic patients with diabetic nephropathy.

MATERIAL AND METHODS

After a 4-week washout period, patients received losartan (100 mg o.d.) and were followed for a mean follow-up of 36 months. At baseline, after 2 and 4 months, and every 6 months thereafter, GFR (51Cr-EDTA-clearance), albuminuria and 24-h blood pressure were determined. The CYP11B2 -344T/C polymorphism was determined by standard polymerase chain reaction (PCR).

RESULTS

The TT, CT and CC genotypes were found in 28 %, 58 % and 14 % of patients, respectively. At baseline albuminuria and blood pressure did not differ between genotype groups. Plasma aldosterone levels (geometric mean (95 % CI)) were similar at baseline: 87 (60-125), 77 (53-112), and 89 (49-161) pg mL(-1) and during follow-up (not significant). After initiation of losartan treatment, comparable mean (SE) reductions in blood pressure and albuminuria were seen in patients with TT, CT and CC genotypes (p >0.6 between groups). After long-term follow-up, there was a tendency towards a difference in systolic blood pressure reduction (p = 0.07, one-way ANOVA), suggesting a poorer response in patients with the CC genotype. No significant difference in rate of decline in GFR (median (range)) was seen between groups (TT, CT, CC): 4.2 (-1.0 to 16.0), 3.2 (-1.6 to 13.8) and 2.6 (-0.1 to 11.0) mL min(-1)year(-1), respectively (p = 0.5).

CONCLUSIONS

Compared to a previous smaller study of angiotensin II receptor blockade in essential hypertension, we could not confirm that CYP11B2 -344T/C genotypes contribute towards explaining the observed variability in response to treatment with angiotensin II receptor blockers, which could be due to lack of power.

Authors+Show Affiliations

Steno Diabetes Center, Gentofte, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

16714246

Citation

Schjoedt, K J., et al. "Aldosterone Synthase (CYP11B2)-344T/C Polymorphism and Renoprotective Response to Losartan Treatment in Diabetic Nephropathy." Scandinavian Journal of Clinical and Laboratory Investigation, vol. 66, no. 3, 2006, pp. 173-80.
Schjoedt KJ, Lajer M, Andersen S, et al. Aldosterone synthase (CYP11B2)-344T/C polymorphism and renoprotective response to losartan treatment in diabetic nephropathy. Scand J Clin Lab Invest. 2006;66(3):173-80.
Schjoedt, K. J., Lajer, M., Andersen, S., Tarnow, L., Rossing, P., & Parving, H. H. (2006). Aldosterone synthase (CYP11B2)-344T/C polymorphism and renoprotective response to losartan treatment in diabetic nephropathy. Scandinavian Journal of Clinical and Laboratory Investigation, 66(3), 173-80.
Schjoedt KJ, et al. Aldosterone Synthase (CYP11B2)-344T/C Polymorphism and Renoprotective Response to Losartan Treatment in Diabetic Nephropathy. Scand J Clin Lab Invest. 2006;66(3):173-80. PubMed PMID: 16714246.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aldosterone synthase (CYP11B2)-344T/C polymorphism and renoprotective response to losartan treatment in diabetic nephropathy. AU - Schjoedt,K J, AU - Lajer,M, AU - Andersen,S, AU - Tarnow,L, AU - Rossing,P, AU - Parving,H-H, PY - 2006/5/23/pubmed PY - 2006/8/1/medline PY - 2006/5/23/entrez SP - 173 EP - 80 JF - Scandinavian journal of clinical and laboratory investigation JO - Scand J Clin Lab Invest VL - 66 IS - 3 N2 - OBJECTIVE: It has been suggested that an aldosterone synthase gene polymorphism (CYP11B2 -344T/C) is predictive of the blood pressure lowering effect of angiotensin II receptor blockers in essential hypertension. We investigated whether this polymorphism is predictive of reductions in blood pressure and albuminuria and preservation of glomerular filtration rate (GFR) during short-term and long-term treatment with losartan in 57 hypertensive type-1 diabetic patients with diabetic nephropathy. MATERIAL AND METHODS: After a 4-week washout period, patients received losartan (100 mg o.d.) and were followed for a mean follow-up of 36 months. At baseline, after 2 and 4 months, and every 6 months thereafter, GFR (51Cr-EDTA-clearance), albuminuria and 24-h blood pressure were determined. The CYP11B2 -344T/C polymorphism was determined by standard polymerase chain reaction (PCR). RESULTS: The TT, CT and CC genotypes were found in 28 %, 58 % and 14 % of patients, respectively. At baseline albuminuria and blood pressure did not differ between genotype groups. Plasma aldosterone levels (geometric mean (95 % CI)) were similar at baseline: 87 (60-125), 77 (53-112), and 89 (49-161) pg mL(-1) and during follow-up (not significant). After initiation of losartan treatment, comparable mean (SE) reductions in blood pressure and albuminuria were seen in patients with TT, CT and CC genotypes (p >0.6 between groups). After long-term follow-up, there was a tendency towards a difference in systolic blood pressure reduction (p = 0.07, one-way ANOVA), suggesting a poorer response in patients with the CC genotype. No significant difference in rate of decline in GFR (median (range)) was seen between groups (TT, CT, CC): 4.2 (-1.0 to 16.0), 3.2 (-1.6 to 13.8) and 2.6 (-0.1 to 11.0) mL min(-1)year(-1), respectively (p = 0.5). CONCLUSIONS: Compared to a previous smaller study of angiotensin II receptor blockade in essential hypertension, we could not confirm that CYP11B2 -344T/C genotypes contribute towards explaining the observed variability in response to treatment with angiotensin II receptor blockers, which could be due to lack of power. SN - 0036-5513 UR - https://www.unboundmedicine.com/medline/citation/16714246/Aldosterone_synthase__CYP11B2__344T/C_polymorphism_and_renoprotective_response_to_losartan_treatment_in_diabetic_nephropathy_ L2 - https://www.tandfonline.com/doi/full/10.1080/00365510600548702 DB - PRIME DP - Unbound Medicine ER -