Division of Population Health Sciences, University of Dundee, Dundee, UK.
Diabet Med. 2013 Oct;30(10):1230-5. doi: 10.1111/dme.12211. Epub 2013 May 14.
To replicate the association of genetic variants with estimated glomerular filtration rate (GFR) and albuminuria, which has been found in recent genome-wide studies in patients with Type 2 diabetes.
We evaluated 16 candidate single nucleotide polymorphisms for estimated GFR in 3028 patients with Type 2 diabetes sampled from clinics across Tayside, Scotland, UK, who were included in the Genetics of Diabetes Audit and Research Tayside (GoDARTs) study. These single nucleotide polymorphisms were tested for their association with estimated GFR at entry to the study, with albuminuria, and with time to stage 3B chronic kidney disease (estimated GFR<45 ml/min/1.73 m(2)). We also stratified the effects on estimated GFR in patients with (n = 2096) and without albuminuria (n = 613).
rs1260326 in GCKR (β=1.30, P = 3.23E-03), rs17319721 in SHROOM3 (β = -1.28, P-value = 3.18E-03) and rs12917707 in UMOD (β = 2.0, P-value = 8.84E-04) were significantly associated with baseline estimated GFR. Analysis of effects on estimated GFR, stratified by albuminuria status, showed that in those without albuminuria (normoalbuminura; n = 613), UMOD had a significantly stronger effect on estimated GFR (β(normo) = 4.03 ± 1.23 vs β(albuminuria) = 1.72 ± 0.76, P = 0.002) compared with those with albuminuria, while GCKR (β(normo) = 0.45 ± 0.89 vs β(albuminuria) = 1.12 ± 0.55, P = 0.08) and SHROOM3 (β(normo) = -0.07 ± 0.89 vs β(albuminuria) = -1.43 ± 0.53, P = 0.003) had a stronger effect on estimated GFR in those with albuminuria. UMOD was also associated with a lower rate of transition to stage 3B chronic kidney disease (hazard ratio = 0.83[0.70, 0.99], P = 0.03).
The genetic variants that regulate estimated GFR in the general population tend to have similar effects in patients with Type 2 diabetes and in this latter population, it is important to adjust for albuminuria status while investigating the genetic determinants of renal function.
复制最近在 2 型糖尿病患者全基因组研究中发现的与估计肾小球滤过率（GFR）和白蛋白尿相关的遗传变异的关联。
我们评估了英国苏格兰泰赛德地区诊所中 3028 名 2 型糖尿病患者的 16 个候选单核苷酸多态性，这些患者纳入了糖尿病审计和研究泰赛德遗传学（GoDARTs）研究。这些单核苷酸多态性在研究入组时与估计的 GFR、白蛋白尿和进展为 3B 期慢性肾病（估计 GFR<45 ml/min/1.73 m(2)）的时间进行了关联测试。我们还对有（n = 2096）和无白蛋白尿（n = 613）的患者的估计 GFR 影响进行了分层。
GCKR 中的 rs1260326（β=1.30，P = 3.23E-03）、SHROOM3 中的 rs17319721（β = -1.28，P 值= 3.18E-03）和 UMOD 中的 rs12917707（β = 2.0，P 值= 8.84E-04）与基线估计的 GFR 显著相关。根据白蛋白尿状态对估计 GFR 的影响进行分析，结果表明在无白蛋白尿（正常白蛋白尿；n = 613）患者中，UMOD 对估计 GFR 的影响明显更强（β（正常白蛋白尿）= 4.03 ± 1.23 vs β（白蛋白尿）= 1.72 ± 0.76，P = 0.002），而 GCKR（β（正常白蛋白尿）= 0.45 ± 0.89 vs β（白蛋白尿）= 1.12 ± 0.55，P = 0.08）和 SHROOM3（β（正常白蛋白尿）= -0.07 ± 0.89 vs β（白蛋白尿）= -1.43 ± 0.53，P = 0.003）对白蛋白尿患者的估计 GFR 影响更强。UMOD 还与较低的进展为 3B 期慢性肾病（危险比= 0.83[0.70，0.99]，P = 0.03）的发生率相关。
在普通人群中调节估计 GFR 的遗传变异在 2 型糖尿病患者中往往具有相似的作用，在后者人群中，在研究肾功能的遗传决定因素时，重要的是要调整白蛋白尿状态。
