Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end-stage diabetic nephropathy
Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end-stage diabetic nephropathy
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DOI：
10.1093/ndt/gfl512
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发表时间：
2007-01-01
影响因子：
6.1
通讯作者：
Kraemer, Bernhard K.
中科院分区：
文献类型：
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作者：
Boeger, Carsten A.;Stubanus, Mike;Kraemer, Bernhard K.
背景MTHFR C677 T单核苷酸多态性TT基因型与血浆同型半胱氨酸水平升高相关，并可能影响心血管死亡率。我们评估了C677 T基因型对一个大型终末期肾病（ESRD）人群死亡率的影响。在德国南部30个透析中心招募的439例终末期糖尿病肾病（DNP）白人患者中确定C677 T基因型。共有482名2型糖尿病患者在入选时没有DNP（无微量白蛋白尿）作为基因型对照组。患者前瞻性随访4年。主要终点为全因死亡率。与对照组相比，病例中的基因型分布不处于Hardy-Weinberg平衡（HWE，P = 0.003），这是由于TT基因型患者的数量少于预期。入选研究前透析治疗时间< 2年的病例符合HWE要求（n = 219）。TT基因型与透析患者体重指数降低（P = 0.002）和糖尿病病程延长（P = 0.03）相关。然而，TT基因型与全因或心源性死亡风险增加无关。此外，我们观察到MTHFR基因型与病例组和对照组的心血管发病率无相关性（P > 0.05），也与进展为新的微量白蛋白尿的发生率增加无相关性。MTHFR 677 TT基因型在我们研究的ESRD患者中的代表性明显不足，但与这些患者的过早死亡率无关。我们没有发现ESRD队列中C677 T基因型导致生存偏倚的证据，也没有发现对照组中基因决定的加速进展为新型微量白蛋白尿导致生存偏倚的证据。然而，我们不能排除TT基因型保护从微量白蛋白尿进展到更晚期的DNP，或者TT基因型与患者进展为ESRD前的过早死亡相关。
Background. The MTHFR C677T single nucleotide polymorphism TT genotype is associated with increased levels of plasma homocysteine and possibly an effect on cardiovascular mortality. We evaluated the effect of C677T genotype on mortality in a large end-stage renal disease (ESRD) cohort.Methods. C677T genotype was determined in 439 Caucasians with end-stage diabetic nephropathy (DNP) (cases) recruited from 30 dialysis centres in Southern Germany. A total of 482 type 2 diabetes patients without DNP (no microalbuminuria) at inclusion served as a genotype control collective. Patients were prospectively followed for 4 years. Primary endpoint was all-cause mortality.Results. In contrast to controls, the genotype distribution in cases was not in Hardy-Weinberg equilibrium (HWE, P = 0.003), due to a less than expected number of patients with the TT genotype. The requirements of HWE were met in cases with < 2 years dialysis therapy prior to study inclusion (n = 219). TT genotype was associated with a decreased body mass index (P = 0.002) and long diabetes duration in dialysis patients (P = 0.03). However, TT genotype was not associated with an increased risk of all-cause or cardiac mortality in the total dialysis collective or the subgroup. Also, we observed no association of MTHFR genotype with cardiovascular morbidity in cases or controls (P > 0.05), or with an increased rate of progression to novel microalbuminuria.Conclusion. MTHFR 677TT genotype was significantly underrepresented in patients with ESRD in our study, but was not associated with premature mortality in these patients. We found no evidence for survival bias due to C677T genotype in the ESRD cohort, or bias due to genetically determined accelerated progression to novel microalbuminuria in the controls. However, we cannot exclude that the TT genotype protects from progression from microalbuminuria to more advanced stages of DNP, or that TT genotype is associated with premature mortality before a patient progresses to ESRD.