Nejentsev Sergey, Cooper Jason D, Godfrey Lisa, Howson Joanna M M, Rance Helen, Nutland Sarah, Walker Neil M, Guja Cristian, Ionescu-Tirgovişte Constantin, Savage David A, Undlien Dag E, Rønningen Kjersti S, Tuomilehto-Wolf Eva, Tuomilehto Jaakko, Gillespie Kathleen M, Ring Susan M, Strachan David P, Widmer Barry, Dunger David, Todd John A
Juvenile Diabetes Research Foundation/Wellcome Trust DiabetesInflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, WT/MRC building, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK.
Diabetes. 2004 Oct;53(10):2709-12. doi: 10.2337/diabetes.53.10.2709.
Vitamin D is known to modulate the immune system, and its administration has been associated with reduced risk of type 1 diabetes. Vitamin D acts via its receptor (VDR). Four single nucleotide polymorphisms (SNPs) of the VDR gene have been commonly studied, and evidence of association with type 1 diabetes has been reported previously. We sequenced the VDR gene region and developed its SNP map. Here we analyzed association of the 98 VDR SNPs in up to 3,763 type 1 diabetic families. First, we genotyped all 98 SNPs in a minimum of 458 U.K. families with two affected offspring. We further tested eight SNPs, including four SNPs associated with P < 0.05 in the first set and the four commonly studied SNPs, in up to 3,305 additional families from the U.K., Finland, Norway, Romania, and U.S. We only found weak evidence of association (P = 0.02-0.05) of the rs4303288, rs12721366, and rs2544043 SNPs. We then tested these three SNPs in an independent set of 1,587 patients and 1,827 control subjects from the U.K. and found no evidence of association. Overall, our results indicate that common sequence variation in the VDR gene has no major effect in type 1 diabetes in the populations tested.
众所周知,维生素D可调节免疫系统,补充维生素D与降低1型糖尿病风险有关。维生素D通过其受体(VDR)发挥作用。VDR基因的四个单核苷酸多态性(SNP)已被广泛研究,此前已有与1型糖尿病相关的报道。我们对VDR基因区域进行了测序并绘制了其SNP图谱。在此,我们分析了多达3763个1型糖尿病家族中98个VDR SNP的关联性。首先,我们对至少458个有两个患病后代的英国家庭中的所有98个SNP进行了基因分型。我们进一步在来自英国、芬兰、挪威、罗马尼亚和美国的多达3305个其他家庭中测试了8个SNP,包括在第一组中P < 0.05的4个SNP以及4个常用研究的SNP。我们仅发现rs4303288、rs12721366和rs2544043这三个SNP存在弱关联证据(P = 0.02 - 0.05)。然后,我们在来自英国的1587例患者和1827例对照受试者的独立样本中对这三个SNP进行了测试,未发现关联证据。总体而言,我们的结果表明,在所测试的人群中,VDR基因的常见序列变异对1型糖尿病没有重大影响。