Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes.
Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes.
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DOI：
10.1093/hmg/ddp522
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发表时间：
2010-02-01
影响因子：
3.5
通讯作者：
Frayling TM
中科院分区：
文献类型：
--
作者：
Perry JR;Weedon MN;Langenberg C;Jackson AU;Lyssenko V;Sparsø T;Thorleifsson G;Grallert H;Ferrucci L;Maggio M;Paolisso G;Walker M;Palmer CN;Payne F;Young E;Herder C;Narisu N;Morken MA;Bonnycastle LL;Owen KR;Shields B;Knight B;Bennett A;Groves CJ;Ruokonen A;Jarvelin MR;Pearson E;Pascoe L;Ferrannini E;Bornstein SR;Stringham HM;Scott LJ;Kuusisto J;Nilsson P;Neptin M;Gjesing AP;Pisinger C;Lauritzen T;Sandbaek A;Sampson M;MAGIC;Zeggini E;Lindgren CM;Steinthorsdottir V;Thorsteinsdottir U;Hansen T;Schwarz P;Illig T;Laakso M;Stefansson K;Morris AD;Groop L;Pedersen O;Boehnke M;Barroso I;Wareham NJ;Hattersley AT;McCarthy MI;Frayling TM
流行病学研究一致表明，2型糖尿病患者的循环性激素结合球蛋白（SHBG）水平低于非糖尿病个体，但这种关联的因果性质存在争议。遗传学研究可以帮助剖析流行病学关联的因果方向，因为基因型不太可能受到疾病过程的混淆、偏见或影响。使用孟德尔随机化原则，我们选择了SHBG基因附近的一个常见单核苷酸多态性（SNP），rs 1799941，与SHBG水平密切相关。我们使用了来自15项研究的27657例2型糖尿病患者和58481例对照的SNP或密切相关的SNP数据。然后，我们使用其他研究的数据来估计2型糖尿病患者和对照组之间SHBG水平的差异。SHBG SNP rs 1799941与2型糖尿病相关[比值比（OR）0.94，95% CI：0.91，0.97; P = 2 × 10−5]，SHBG升高等位基因与2型糖尿病风险降低相关。考虑到SHBG-SNP与SHBG水平的相关性（SHBG水平每拷贝A等位基因高0.2个标准差）和SHBG水平与2型糖尿病的相关性（SHBG水平在2型糖尿病患者中比对照组低0.23个标准差），该效应与预期非常相似（OR 0.92，95%CI：0.88，0.96）。男性和女性的结果非常相似。没有证据表明这种变异与糖尿病相关的中间性状有关，包括胰岛素分泌和抵抗的几个指标。我们的研究结果，以及最近另一项遗传学研究的结果，加强了SHBG和性激素参与2型糖尿病病因学的证据。
Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiological associations because genotypes are much less likely to be confounded, biased or influenced by disease processes. Using this Mendelian randomization principle, we selected a common single nucleotide polymorphism (SNP) near the SHBG gene, rs1799941, that is strongly associated with SHBG levels. We used data from this SNP, or closely correlated SNPs, in 27 657 type 2 diabetes patients and 58 481 controls from 15 studies. We then used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The SHBG SNP rs1799941 was associated with type 2 diabetes [odds ratio (OR) 0.94, 95% CI: 0.91, 0.97; P = 2 × 10−5], with the SHBG raising allele associated with reduced risk of type 2 diabetes. This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls). Results were very similar in men and women. There was no evidence that this variant is associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes.
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影响因子：
4.5
作者：
Melzer D;Perry JR;Hernandez D;Corsi AM;Stevens K;Rafferty I;Lauretani F;Murray A;Gibbs JR;Paolisso G;Rafiq S;Simon-Sanchez J;Lango H;Scholz S;Weedon MN;Arepalli S;Rice N;Washecka N;Hurst A;Britton A;Henley W;van de Leemput J;Li R;Newman AB;Tranah G;Harris T;Panicker V;Dayan C;Bennett A;McCarthy MI;Ruokonen A;Jarvelin MR;Guralnik J;Bandinelli S;Frayling TM;Singleton A;Ferrucci L
通讯作者：
Ferrucci L
影响因子：
7.7
作者：
Freathy RM;Timpson NJ;Lawlor DA;Pouta A;Ben-Shlomo Y;Ruokonen A;Ebrahim S;Shields B;Zeggini E;Weedon MN;Lindgren CM;Lango H;Melzer D;Ferrucci L;Paolisso G;Neville MJ;Karpe F;Palmer CN;Morris AD;Elliott P;Jarvelin MR;Smith GD;McCarthy MI;Hattersley AT;Frayling TM
通讯作者：
Frayling TM
影响因子：
9.8
作者：
Corrales, JJ;Burgo, RM;Miralles, JM
通讯作者：
Miralles, JM
影响因子：
5.8
作者：
Pasquali, R;Gambineri, A;Morselli-Labate, AM
通讯作者：
Morselli-Labate, AM
影响因子：
7.7
作者：
Brennan, Paul;McKay, James;Smith, George Davey
通讯作者：
Smith, George Davey