Coto Eliecer, Díaz-Corte Carmen, Tranche Salvador, Gómez Juan, Alonso Belén, Iglesias Sara, Reguero Julián R, López-Larrea Carlos, Coto-Segura Pablo
Genética Molecular-Laboratorio Medicina, HUCA, Oviedo, Spain; Universidad de Oviedo, Oviedo, Spain; RED INVESTIGACION RENAL (REDINREN), Madrid, Spain; Instituto de Investigación Sanitaria del Principado de Asturias-ISPA, Oviedo, Spain.
Nefrología, HUCA, Oviedo, Spain; Universidad de Oviedo, Oviedo, Spain; RED INVESTIGACION RENAL (REDINREN), Madrid, Spain.
Hum Immunol. 2018 Jun;79(6):494-498. doi: 10.1016/j.humimm.2018.03.008. Epub 2018 Mar 27.
The NF-kappaB pathway might play a role in the pathogenesis of renal disease and type 2 diabetes (T2DM). Our aim was to determine whether common polymorphisms in NF-kappaB genes were associated with impaired renal function and T2DM in a cohort of healthy elderly individuals. We studied 487 individuals, all Caucasian and aged 65-85 years. A total of 104 (21%) had impaired renal function (estimated glomerular filtration rate, eGFR < 60) and 146 (30%) were classified as diabetics. The genotypes of 4 common variants were determined through PCR-RFLP or fluorescent capillary electrophoresis. The NFKB1 variants were significantly associated with T2DM: rs7667496 p = 0.01, OR = 1.68; and rs28362491 p = 0.02, OR = 1.67. They remained significantly associated in a multiple logistic regression with age, gender, hypertension, body mass index, and cholesterol. There was a trend toward the association of these variants with eGFR < 60. The two NFKB1 variants were in linkage disequilibrium (D' = -0.86), and homozygous for the two non-risk alleles (rs7667496 CC + rs28362491 II), were significantly more common in the non-diabetics (p = 0.02). In our cohort the NFKB1 variation was an independent risk factor for developing T2DM. Additional studies to confirm this association are of special interest, as well as studies to give a functional explanation to the genetic association.
核因子κB（NF-κB）信号通路可能在肾脏疾病和2型糖尿病（T2DM）的发病机制中发挥作用。我们的目的是确定NF-κB基因的常见多态性是否与健康老年人群的肾功能损害和T2DM相关。我们研究了487名个体，均为65至85岁的白种人。共有104人（21%）肾功能受损（估计肾小球滤过率，eGFR＜60），146人（30%）被归类为糖尿病患者。通过聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）或荧光毛细管电泳确定了4个常见变异的基因型。NFKB1变异与T2DM显著相关：rs7667496 p = 0.01，比值比（OR）= 1.68；rs28362491 p = 0.02，OR = 1.67。在对年龄、性别、高血压、体重指数和胆固醇进行多因素逻辑回归分析时，它们仍具有显著相关性。这些变异与eGFR＜60存在关联趋势。两个NFKB1变异处于连锁不平衡状态（D' = -0.86），两个非风险等位基因（rs7667496 CC + rs28362491 II）的纯合子在非糖尿病患者中更为常见（p = 0.02）。在我们的队列中，NFKB1变异是发生T2DM的独立危险因素。进一步研究以证实这种关联以及对这种遗传关联进行功能解释的研究具有特殊意义。
