Investigation of known estimated glomerular filtration rate loci in patients with type 2 diabetes.
Investigation of known estimated glomerular filtration rate loci in patients with type 2 diabetes.
复制标题
DOI：
10.1111/dme.12211
复制
发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Colhoun HM
中科院分区：
文献类型：
--
作者：
Deshmukh HA;Palmer CN;Morris AD;Colhoun HM
复制遗传变异与估计肾小球滤过率 (GFR) 和白蛋白尿之间的关联，最近在 2 型糖尿病患者的全基因组研究中发现了这种关联。我们评估了 3028 名 2 型糖尿病患者的估计 GFR 的 16 个候选单核苷酸多态性，这些患者来自英国苏格兰泰赛德的诊所，这些患者被纳入泰赛德糖尿病遗传学审计和研究 (GoDARTs) 研究。测试了这些单核苷酸多态性与进入研究时估计的 GFR、白蛋白尿以及达到 3B 期慢性肾病的时间（估计的 GFR<45 ml/min/1.73 m2）的相关性。我们还对有蛋白尿的患者 (n = 2096) 和无蛋白尿的患者 (n = 613) 的估计 GFR 的影响进行了分层。 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 GFR 显着相关。按白蛋白尿状态分层对估计 GFR 的影响分析显示，在无白蛋白尿的患者（正常白蛋白尿；n = 613）中，与有白蛋白尿的患者相比，UMOD 对估计 GFR 的影响显着更强（β 正常 = 4.03 ± 1.23 对比 β 白蛋白尿 = 1.72 ± 0.76，P = 0.002），而 GCKR (β 正常= 0.45 ± 0.89 vs β白蛋白尿 = 1.12 ± 0.55，P = 0.08）和 SHROOM3（βnormo = -0.07 ± 0.89 vs β白蛋白尿 = -1.43 ± 0.53，P = 0.003）对蛋白尿患者的估计 GFR 有更强的影响。 UMOD 还与较低的 3B 期慢性肾病转化率相关（风险比 = 0.83[0.70, 0.99]，P = 0.03）。一般人群中调节估计 GFR 的遗传变异往往对 2 型糖尿病患者产生类似的影响，在后一人群中，在研究肾功能的遗传决定因素时调整白蛋白尿状态非常重要。
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 m2). 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 (βnormo = 4.03 ± 1.23 vs βalbuminuria = 1.72 ± 0.76, P = 0.002) compared with those with albuminuria, while GCKR (βnormo = 0.45 ± 0.89 vs βalbuminuria = 1.12 ± 0.55, P = 0.08) and SHROOM3 (βnormo = −0.07 ± 0.89 vs βalbuminuria = −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.
登录
查看更多内容
影响因子：
16.2
作者：
MacIsaac, R;Tsalamandris, C;Jerums, G
通讯作者：
Jerums, G
估计肾小球滤过率和尿液中尿嘧啶浓度与 UMOD 基因区域测序发现的罕见变异的关系
影响因子：
3.7
作者：
Koettgen, Anna;Yang, Qiong;Fox, Caroline S.
通讯作者：
Fox, Caroline S.
影响因子：
16.2
作者：
Bonetti S;Trombetta M;Boselli ML;Turrini F;Malerba G;Trabetti E;Pignatti PF;Bonora E;Bonadonna RC
通讯作者：
Bonadonna RC
影响因子：
--
作者：
Reznichenko, Anna;Boeger, Carsten A.;Navis, Gerjan
通讯作者：
Navis, Gerjan
影响因子：
3.5
作者：
Ellis, Jaclyn W.;Chen, Ming-Huei;O'Seaghdha, Conall M.
通讯作者：
O'Seaghdha, Conall M.