TNFRSF1B 变异与印度欧罗巴血统的 2 型糖尿病无关。
No association of TNFRSF1B variants with type 2 diabetes in Indians of Indo-European origin.
机构信息
Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
出版信息
BMC Med Genet. 2011 Aug 17;12:110. doi: 10.1186/1471-2350-12-110.
BACKGROUND
There has been no systematic evaluation of the association between genetic variants of type 2 receptor for TNFα (TNFR2) and type 2 diabetes, despite strong biological evidence for the role of this receptor in the pathogenesis of this complex disorder. In view of this, we performed a comprehensive association analysis of TNFRSF1B variants with type 2 diabetes in 4,200 Indo-European subjects from North India.
METHODS
The initial phase evaluated association of seven SNPs viz. rs652625, rs496888, rs6697733, rs945439, rs235249, rs17883432 and rs17884213 with type 2 diabetes in 2,115 participants (1,073 type 2 diabetes patients and 1,042 control subjects). Further, we conducted replication analysis of three associated SNPs in 2,085 subjects (1,047 type 2 diabetes patients and 1,038 control subjects).
RESULTS
We observed nominal association of rs945439, rs235249 and rs17884213 with type 2 diabetes (P < 0.05) in the initial phase. Haplotype CC of rs945439 and rs235249 conferred increased susceptibility for type 2 diabetes [OR = 1.19 (95%CI 1.03-1.37), P = 0.019/Pperm = 0.076] whereas, TG haplotype of rs235249 and rs17884213 provided protection against type 2 diabetes [OR = 0.83 (95%CI 0.72-0.95, P = 7.2 × 10-3/Pperm = 0.019]. We also observed suggestive association of rs496888 with plasma hsCRP levels [P = 0.042]. However, the association of rs945439, rs235249 and rs17884213 with type 2 diabetes was not replicated in the second study population. Meta-analysis of the two studies also failed to detect any association with type 2 diabetes.
CONCLUSIONS
Our two-stage association analysis suggests that TNFRSF1B variants are not the determinants of genetic risk of type 2 diabetes in North Indians.
背景
尽管有强有力的生物学证据表明该受体在这种复杂疾病的发病机制中起作用，但目前还没有对 2 型肿瘤坏死因子受体（TNFR2）的遗传变异与 2 型糖尿病之间的关联进行系统评估。有鉴于此，我们在来自印度北部的 4200 名印欧人群中进行了 TNFRSF1B 变体与 2 型糖尿病的综合关联分析。
方法
在初始阶段，我们评估了七个单核苷酸多态性（SNP）与 2 型糖尿病的关联，分别是 rs652625、rs496888、rs6697733、rs945439、rs235249、rs17883432 和 rs17884213，涉及 2115 名参与者（1073 名 2 型糖尿病患者和 1042 名对照者）。然后，我们在 2085 名参与者（1047 名 2 型糖尿病患者和 1038 名对照者）中进行了三个相关 SNP 的复制分析。
结果
在初始阶段，我们观察到 rs945439、rs235249 和 rs17884213 与 2 型糖尿病存在显著关联（P < 0.05）。rs945439 和 rs235249 的 CC 单倍型增加了 2 型糖尿病的易感性[比值比（OR）= 1.19（95%置信区间（CI）1.03-1.37），P = 0.019/perm P = 0.076]，而 rs235249 和 rs17884213 的 TG 单倍型则降低了 2 型糖尿病的风险[OR = 0.83（95%CI 0.72-0.95，P = 7.2 × 10-3/perm P = 0.019]。我们还观察到 rs496888 与血浆 hsCRP 水平呈显著相关[P = 0.042]。然而，rs945439、rs235249 和 rs17884213 与 2 型糖尿病的关联在第二研究人群中未得到复制。两项研究的荟萃分析也未能检测到与 2 型糖尿病的任何关联。
结论
我们的两阶段关联分析表明，TNFRSF1B 变体不是北印度人 2 型糖尿病遗传风险的决定因素。
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