The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies.
The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies.
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DOI：
10.1186/1471-2350-9-45
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发表时间：
2008-05-22
影响因子：
--
通讯作者：
Meyre D
中科院分区：
文献类型：
--
作者：
Cauchi S;Nead KT;Choquet H;Horber F;Potoczna N;Balkau B;Marre M;Charpentier G;Froguel P;Meyre D
考虑到先前重复研究中的部分异质性可能是由于病例对照设计中肥胖受试者的可变比例所致，我们评估了肥胖和非肥胖受试者中遗传变异与2型糖尿病（T2 D）的相关性。我们对1，283名血糖正常（NG）和1，581名T2 D肥胖个体以及3，189名NG和1，244名T2 D非肥胖欧洲血统受试者进行了RETN、KCNJ 11、HNF 4A、HNF 1A、GCK、SLC 30 A8、ENPP 1、ADIPOQ、PPARG和TCF 7 L2多态性基因分型，使我们能够在广泛的BMI范围内检查T2 D风险。在非肥胖个体中，我们观察到HNF 1A I27 L与T2 D显著相关[比值比（OR）= 1.14，P = 0.04]，GCK-30 G>A（OR = 1.23，P = 0.01），SLC30A8 R325W（OR = 0.87，P = 0.04），TCF7L2 rs7903146（OR = 1.89，P = 4.5 × 10-23），与PPARG Pro 12 Ala无显著相关性ADIPOQ-11，377 C>G（OR = 1.00，P = 0.97）和ENPP1 K121 Q（OR = 0.99，P = 0.94）。在肥胖受试者中，用PPARG Pro 12 Ala检测与T2 D的相关性（OR = 0.73，P = 0.004），ADIPOQ-11，377 C>G（OR = 1.26，P = 0.02），ENPP1 K121Q（OR = 1.30，P = 0.003）和TCF 7 L2 rs7903146（OR = 1.30，P = 1.1 × 10-4），与HNF 1A I27 L无显著相关性GCK-30G>A（OR = 1.15，P = 0.12）和SLC 30A8 R325W（OR = 0.95，P = 0.44）。然而，仅在TCF 7 L2 rs7903146（P = 3.2 × 10-5）和ENPP 1 K121 Q（P = 0.02）中发现了基因型异质性。在非肥胖或肥胖个体中，未发现KCNJ 11、RETN和HNF 4A多态性与T2 D相关。调节胰岛素作用的遗传变异可能对肥胖患者的T2 D易感性产生更大的影响，而作用于胰岛素分泌的遗传变异可能对非肥胖个体的T2 D易感性产生更大的影响。
Considering that a portion of the heterogeneity amongst previous replication studies may be due to a variable proportion of obese subjects in case-control designs, we assessed the association of genetic variants with type 2 diabetes (T2D) in large groups of obese and non-obese subjects. We genotyped RETN, KCNJ11, HNF4A, HNF1A, GCK, SLC30A8, ENPP1, ADIPOQ, PPARG, and TCF7L2 polymorphisms in 1,283 normoglycemic (NG) and 1,581 T2D obese individuals as well as in 3,189 NG and 1,244 T2D non-obese subjects of European descent, allowing us to examine T2D risk over a wide range of BMI. Amongst non-obese individuals, we observed significant T2D associations with HNF1A I27L [odds ratio (OR) = 1.14, P = 0.04], GCK -30G>A (OR = 1.23, P = 0.01), SLC30A8 R325W (OR = 0.87, P = 0.04), and TCF7L2 rs7903146 (OR = 1.89, P = 4.5 × 10-23), and non-significant associations with PPARG Pro12Ala (OR = 0.85, P = 0.14), ADIPOQ -11,377C>G (OR = 1.00, P = 0.97) and ENPP1 K121Q (OR = 0.99, P = 0.94). In obese subjects, associations with T2D were detected with PPARG Pro12Ala (OR = 0.73, P = 0.004), ADIPOQ -11,377C>G (OR = 1.26, P = 0.02), ENPP1 K121Q (OR = 1.30, P = 0.003) and TCF7L2 rs7903146 (OR = 1.30, P = 1.1 × 10-4), and non-significant associations with HNF1A I27L (OR = 0.96, P = 0.53), GCK -30G>A (OR = 1.15, P = 0.12) and SLC30A8 R325W (OR = 0.95, P = 0.44). However, a genotypic heterogeneity was only found for TCF7L2 rs7903146 (P = 3.2 × 10-5) and ENPP1 K121Q (P = 0.02). No association with T2D was found for KCNJ11, RETN, and HNF4A polymorphisms in non-obese or in obese individuals. Genetic variants modulating insulin action may have an increased effect on T2D susceptibility in the presence of obesity, whereas genetic variants acting on insulin secretion may have a greater impact on T2D susceptibility in non-obese individuals.
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影响因子：
3.7
作者：
Liang J;Fu M;Ciociola E;Chandalia M;Abate N
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作者：
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影响因子：
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作者：
Hinds, DA;Stuve, LL;Cox, DR
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