Whole exome sequencing identifies variation in CYB5A and RNF10 associated with adiposity and type 2 diabetes.
Whole exome sequencing identifies variation in CYB5A and RNF10 associated with adiposity and type 2 diabetes.
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DOI：
10.1002/oby.20647
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发表时间：
2014-04
期刊：
影响因子：
6.9
通讯作者：
Baier, Leslie J.
中科院分区：
文献类型：
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作者：
Huang, Ke;Nair, Anup K.;Muller, Yunhua Li;Piaggi, Paolo;Bian, Li;del Rosario, Melissa;Knowler, William C.;Kobes, Sayuko;Hanson, Robert L.;Bogardus, Clifton;Baier, Leslie J.
与 2 型糖尿病 (T2D) 相关的基因中已发现的编码变异很少，而且易感基因影响 T2D 风险的潜在生理机制通常未知。本研究的目的是确定通过影响糖尿病前期特征而增加 T2D 风险的编码变异。对 177 名皮马印第安人进行了全外显子组测序。对 555 名受试者的选定变异 (N = 345) 进行了基因分型，这些受试者的特征包括身体脂肪、钳夹期间的葡萄糖处理率、对葡萄糖的急性胰岛素反应以及 OGTT 期间的 2 小时血浆葡萄糖浓度，并且还在多达 5,880 名具有 BMI 纵向测量的受试者中进行了基因分型。在 7,667 名受试者中评估了与数量性状相关的变异与 T2D 的关系。 CYB5A 中的 rs7238987 与身体肥胖相关（p=7.0×10−6）。该 SNP 和 RNF10 中的新 SNP 还与最大记录 BMI（p=6.2×10−7 和 p=7.2×10−4）和最大儿童 BMI z 分数（p=5.9×10−4 和 p=8.5×10−7）相关。 BMI 增加的等位基因增加 T2D 的风险（p= 0.01；OR=1.13 [1.03–1.24] 和 9.5×10−3，OR=1.49 [1.10–2.02]）。 CYB5A 在硬脂酰辅酶 A 去饱和酶活性中发挥作用，而 RNF10 在体重调节途径中的作用未知，与肥胖和名义上增加的美洲印第安人 T2D 风险相关。
Few coding variants in genes associated with type 2 diabetes (T2D) have been identified, and the underlying physiologic mechanisms whereby susceptibility genes influence T2D risk are often unknown. The objective of this study was to identify coding variation that increases risk for T2D via an effect on a pre-diabetic trait. Whole exome sequencing was done in 177 Pima Indians. Selected variants (N=345) were genotyped in 555 subjects characterized for body fatness, glucose disposal rates during a clamp, acute insulin response to glucose, and 2-hour plasma glucose concentrations during an OGTT, and were also genotyped in up to 5,880 subjects with longitudinal measures of BMI. Variants associated with quantitative traits were assessed for association with T2D in 7,667 subjects. rs7238987 in CYB5A associated with body fatness (p=7.0×10−6). This SNP and a novel SNP in RNF10 also associated with maximum recorded BMI (p=6.2×10−7 and p=7.2×10−4) and maximum childhood BMI z-score (p=5.9×10−4 and p=8.5×10−7). The BMI increasing alleles increased risk for T2D (p= 0.01; OR=1.13 [1.03–1.24] and 9.5×10−3, OR=1.49 [1.10–2.02]). CYB5A, which has a role in stearyl-CoA-desaturase activity, and RNF10, with an unknown role in weight regulating pathways, associated with adiposity and nominally increased risk for T2D in American Indians.
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影响因子：
30.8
作者：
通讯作者：
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影响因子：
64.8
作者：
Skarnes WC;Rosen B;West AP;Koutsourakis M;Bushell W;Iyer V;Mujica AO;Thomas M;Harrow J;Cox T;Jackson D;Severin J;Biggs P;Fu J;Nefedov M;de Jong PJ;Stewart AF;Bradley A
通讯作者：
Bradley A
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
作者：
通讯作者：
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DOI：
10.1073/pnas.132384699
发表时间：
2002-08-20
影响因子：
11.1
作者：
Ntambi, JM;Miyazaki, M;Attie, AD
通讯作者：
Attie, AD