SLC22A2 基因 808 G/T 变异与中国 2 型糖尿病患者服用二甲双胍后血浆乳酸浓度有关。
SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin.
机构信息
Department of Endocrinology and Metabolism, Shanghai Jiaotong University affiliated Sixth People's Hospital, China.
出版信息
Acta Pharmacol Sin. 2010 Feb;31(2):184-90. doi: 10.1038/aps.2009.189.
AIM
To investigate the potential relationship between the SLC22A2 gene polymorphism and blood lactate concentration in Shanghai Hans suffering from type 2 diabetes mellitus (T2DM).
METHODS
The SLC22A2 single nucleotide polymorphism (SNP) 808G/T was genotyped in 400 T2DM patients, including a metformin-treated group (n=200) and a non-metformin-treated group (n=200). Fasting plasma lactic acid levels were measured with an enzyme-electrode assay. Biochemical indexes, including plasma alanine aminotransferase (ALT), creatinine (Cr), and glycolated hemoglobin (HbA1c), were also measured.
RESULTS
The fasting plasma lactate concentration in the metformin-treated group was significantly higher than that in the non-metformin-treated group (1.29+/-0.45 mmol/L vs 1.18+/-0.44 mmol/L, P=0.015). Additionally, the ratio of patients with hyperlactacidemia was 8% (16/200) for the metformin-treated group and 5.5% (11/200) for the non-metformin-treated group, with no lactic acidosis found in either group. The frequency of the SLC22A2 808G/T T allele was 12.9%. Patients with the mutant genotype (TT) had a higher blood lactate concentration in the metformin-treated group than those in the non-metformin-treated group (t=2.492, P=0.013). This trend was not observed in the GG and GT genotypes when compared with metformin-treated and non-metformin-treated groups. Patients with the mutant genotype (TT) in the metformin-treated group also had a higher incidence of hyperlactacidemia compared with the GG genotype (40.0% vs 6.9%, P=0.050) in the metformin-treated group and the GG (6.0%, P=0.042) or GT (4.3%, P=0.043) genotypes in the non-metformin-treated group. In the metformin-treated group, there were significant gender differences in lactate concentrations in the TT (2.18+/-0.15 vs 1.04+/-0.27 mmol/L, P=0.008) and GG genotypes (1.40+/-0.51 vs 1.19+/-0.35 mmol/L, P=0.004). The lactate levels of women with the TT genotype were the highest in the metformin-treated group, but differences in lactate levels among the genotypes were not observed in the non-metformin-treated group.
CONCLUSION
There is an 808G/T polymorphism in the SLC22A2 gene in Chinese Hans with T2DM. The 808G>T variance in the SLC22A2 gene can affect the plasma lactate level and the incidence of hyperlactacidemia in T2DM patients undergoing metformin therapy. Additionally, the female patients carrying the TT genotype are prone to lactatemia.
目的
探讨上海汉族 2 型糖尿病（T2DM）患者 SLC22A2 基因多态性与血乳酸浓度的潜在关系。
方法
对 400 例 T2DM 患者（包括使用二甲双胍治疗的患者 200 例和未使用二甲双胍治疗的患者 200 例）进行 SLC22A2 单核苷酸多态性（SNP）808G/T 基因分型。采用酶电极法测定空腹血乳酸水平。同时测定生化指标，包括血浆丙氨酸氨基转移酶（ALT）、肌酐（Cr）和糖化血红蛋白（HbA1c）。
结果
使用二甲双胍治疗的患者空腹血乳酸浓度明显高于未使用二甲双胍治疗的患者（1.29±0.45mmol/L 比 1.18±0.44mmol/L，P=0.015）。此外，使用二甲双胍治疗的患者中高乳酸血症的发生率为 8%（16/200），未使用二甲双胍治疗的患者中高乳酸血症的发生率为 5.5%（11/200），两组均未发现乳酸性酸中毒。SLC22A2 808G/T T 等位基因的频率为 12.9%。与未使用二甲双胍治疗的患者相比，使用二甲双胍治疗且携带突变基因型（TT）的患者血乳酸浓度更高（t=2.492，P=0.013）。在 GG 和 GT 基因型中未观察到这种趋势。与携带 GG 基因型的患者相比，使用二甲双胍治疗且携带突变基因型（TT）的患者发生高乳酸血症的比例更高（40.0%比 6.9%，P=0.050），且携带 TT 基因型的患者发生高乳酸血症的比例高于携带 GG（6.0%，P=0.042）或 GT（4.3%，P=0.043）基因型的患者。在使用二甲双胍治疗的患者中，TT 基因型（2.18±0.15比 1.04±0.27mmol/L，P=0.008）和 GG 基因型（1.40±0.51比 1.19±0.35mmol/L，P=0.004）之间的乳酸浓度存在显著的性别差异。携带 TT 基因型的女性患者的乳酸水平最高，但在未使用二甲双胍治疗的患者中，不同基因型之间的乳酸水平无差异。
结论
中国汉族 2 型糖尿病患者中存在 SLC22A2 基因 808G/T 多态性。SLC22A2 基因的 808G>T 变异可影响接受二甲双胍治疗的 T2DM 患者的血浆乳酸水平和高乳酸血症的发生率。此外，携带 TT 基因型的女性患者易发生乳酸性血症。
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