Association of the TNF-a-C-857T Polymorphism With Resistance to the Cholesterol-Lowering Effect of HMG-CoA Reductase Inhibitors in Type 2 Diabetic Subjects  

Oleh:

Takahashi, Toru ; Takahashi, Kazuma ; Yamashina, Mitsuhiro ; Maesawa, Chihaya

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Diabetes Care vol. 33 no. 03 (Mar. 2010), page 463-466.
Topik: DIABETES; DIABETES MELLITUS; TNF-a-C-857T Polymorphism; Resistance; Cholesterol-Lowering; HMG-CoA Reductase Inhibitors; Type 2 Diabetic Subjects

Ketersediaan

Perpustakaan FK Nomor Panggil: D05.K.2010.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

OBJECTIVE : An association of the C-857T polymorphism of the tumor necrosis factor-a (TNF-a) gene promoter region with LDL cholesterol levels has been reported. This study was designed to evaluate the relationship between the TNF-a-C-857T polymorphism and LDL cholesterol levels according to statin treatment in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS : DNA was obtained from 322 Japanese subjects (160 male and 162 female) with type 2 diabetes, and TNF-a-C-857T polymorphisms were determined by direct sequencing. Serum LDL cholesterol was measured by a direct method. RESULTS : Although serum LDL cholesterol levels were significantly higher in the T carriers (C/T + T/T) than in the non–T carriers (C/C) (3.14 ± 0.86 vs. 2.89 ± 0.75 mmol/l, P < 0.05), there was no difference in LDL cholesterol levels between the non–T carriers and the T carriers in statin-untreated subjects (2.87 ± 0.73 vs. 2.89 ± 0.76 mmol/l, NS), whereas in statin-treated subjects, LDL cholesterol levels were significantly higher in the T carriers than in the non–T carriers (3.43 ± 0.89 vs. 2.90 ± 0.78 mmol/l, P = 0.0007). There were no differences in HDL cholesterol and triglyceride levels between the non–T carriers and the T carriers in both statin-treated and -untreated subjects. The percent decrease in LDL cholesterol levels after administration of statins was significantly smaller in the T carriers compared with the non–T carriers (27.6 vs. 36.4%, P = 0.031). CONCLUSIONS : The mutant allele of the C-857T promoter polymorphism of the TNF-a gene may predispose to resistance to the LDL cholesterol–lowering effect of statins and could be one of the markers used to predict the efficacy of statins.

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