Genetically elevated fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes: the cardiovascular health study.
Genetically elevated fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes: the cardiovascular health study.
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DOI：
10.2337/dc12-2323
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发表时间：
2013-10
期刊：
影响因子：
16.2
通讯作者：
Mukamal KJ
中科院分区：
文献类型：
--
作者：
Jensen MK;Bartz TM;Djoussé L;Kizer JR;Zieman SJ;Rimm EB;Siscovick DS;Psaty BM;Ix JH;Mukamal KJ
胎球蛋白A水平与2型糖尿病的高风险相关，但这种关联是否是因果关系尚不清楚。我们调查了胎球蛋白A基因（AHSG）中常见（>5%）的遗传变异、胎球蛋白A水平、空腹血糖和2型糖尿病风险。1992-1993年，对2,893名65岁以上的高加索人和542名65岁以上的非洲裔美国人的遗传变异、胎球蛋白A水平和空腹血糖进行了评估。常见的AHSG变体（rs 4917和rs 2248690）与胎球蛋白A浓度密切相关（P < 0.0001）。在对259例2型糖尿病发病病例的分析中，单核苷酸多态性（SNP）与随访期间的糖尿病风险无关，当纳入579例流行病例时，观察到类似的无效关联。正如预期的那样，较高的胎球蛋白A水平与较高的空腹血糖浓度相关（高加索人每SD高1.9 mg/dL [95% CI，1.2-2.7]），但使用两种SNP作为测量胎球蛋白A的无偏替代的孟德尔随机化分析不支持遗传预测的胎球蛋白A水平与空腹血糖之间的关联（高加索人中每SD低-0.3 mg/dL [95% CI，-1.9至1.3]）。空腹血糖与实际和遗传预测的胎球蛋白A水平之间的差异具有统计学意义（P = 0.001）。在较小的非裔美国人样本中，结果趋势相似，但在统计学上不显著。AHSG基因的常见变异与血浆胎球蛋白A浓度密切相关，但与2型糖尿病或葡萄糖浓度的风险无关，这增加了胎球蛋白A与2型糖尿病之间可能不是因果关系的可能性。
Fetuin-A levels are associated with higher risk of type 2 diabetes, but it is unknown if the association is causal. We investigated common (>5%) genetic variants in the fetuin-A gene (AHSG) fetuin-A levels, fasting glucose, and risk of type 2 diabetes. Genetic variation, fetuin-A levels, and fasting glucose were assessed in 2,893 Caucasian and 542 African American community-living individuals 65 years of age or older in 1992–1993. Common AHSG variants (rs4917 and rs2248690) were strongly associated with fetuin-A concentrations (P < 0.0001). In analyses of 259 incident cases of type 2 diabetes, the single nucleotide polymorphisms (SNPs) were not associated with diabetes risk during follow-up and similar null associations were observed when 579 prevalent cases were included. As expected, higher fetuin-A levels were associated with higher fasting glucose concentrations (1.9 mg/dL [95% CI, 1.2–2.7] higher per SD in Caucasians), but Mendelian randomization analyses using both SNPs as unbiased proxies for measured fetuin-A did not support an association between genetically predicted fetuin-A levels and fasting glucose (−0.3 mg/dL [95% CI, −1.9 to 1.3] lower per SD in Caucasians). The difference between the associations of fasting glucose with actual and genetically predicted fetuin-A level was statistically significant (P = 0.001). Results among the smaller sample of African Americans trended in similar directions but were statistically insignificant. Common variants in the AHSG gene are strongly associated with plasma fetuin-A concentrations, but not with risk of type 2 diabetes or glucose concentrations, raising the possibility that the association between fetuin-A and type 2 diabetes may not be causal.
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影响因子：
7.7
作者：
Stefan, Norbert;Fritsche, Andreas;Weikert, Cornelia;Boeing, Heiner;Joost, Hans-Georg;Haring, Hans-Ulrich;Schulze, Matthias B.
通讯作者：
Schulze, Matthias B.
影响因子：
7.7
作者：
Andersen, Gitte;Burgdorf, Kristoffer Solvsten;Pedersen, Oluf
通讯作者：
Pedersen, Oluf
影响因子：
7.2
作者：
PSATY, BM;LEE, M;LYLES, M
通讯作者：
LYLES, M
DOI：
10.1161/circgenetics.109.882696
发表时间：
2010-06
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Musunuru K;Lettre G;Young T;Farlow DN;Pirruccello JP;Ejebe KG;Keating BJ;Yang Q;Chen MH;Lapchyk N;Crenshaw A;Ziaugra L;Rachupka A;Benjamin EJ;Cupples LA;Fornage M;Fox ER;Heckbert SR;Hirschhorn JN;Newton-Cheh C;Nizzari MM;Paltoo DN;Papanicolaou GJ;Patel SR;Psaty BM;Rader DJ;Redline S;Rich SS;Rotter JI;Taylor HA Jr;Tracy RP;Vasan RS;Wilson JG;Kathiresan S;Fabsitz RR;Boerwinkle E;Gabriel SB;NHLBI Candidate Gene Association Resource
通讯作者：
NHLBI Candidate Gene Association Resource
影响因子：
64.5
作者：
AUBERGER, P;FALQUERHO, L;LECAM, A
通讯作者：
LECAM, A