Association of variants in RETN with plasma resistin levels and diabetes-related traits in the Framingham Offspring Study.
Association of variants in RETN with plasma resistin levels and diabetes-related traits in the Framingham Offspring Study.
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DOI：
10.2337/db08-1339
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发表时间：
2009-03
期刊：
影响因子：
7.7
通讯作者：
Florez, Jose C.
中科院分区：
文献类型：
--
作者：
Hivert, Marie-France;Manning, Alisa K.;McAteer, Jarred B.;Dupuis, Josee;Fox, Caroline S.;Cupples, L. Adrienne;Meigs, James B.;Florez, Jose C.
目的-RETN基因编码脂肪因子β-内酰胺酶。RETN与血浆β-淀粉样蛋白水平、2型糖尿病和相关代谢特征的关系一直不一致。利用综合连锁不平衡作图，我们对RETN的标签单核苷酸多态性（SNP）进行基因分型，并检测其与血浆谷氨酰胺水平、糖尿病风险和血糖性状的相关性。研究设计和方法-我们对2,531名FRA后代研究参与者进行了为期28年的随访，检查了他们的血糖水平、血糖表型和糖尿病发病率。我们对21个标签SNP进行了基因分型，这些标签SNP捕获了RETN及其侧翼区域中r2 > 0.8的常见（次要等位基因频率>0.05）或先前报道的SNP。我们使用性别和年龄调整的线性混合效应模型（有/没有BMI调整）来检验SNP与性状的加性关联，调整考克斯比例风险模型解释糖尿病事件的相关性，并生成经验P值（Pe）来控制1型错误。结果：RETN 3′端的4个标签SNP（rs 1477341、rs 4804765、rs 1423096和rs 10401670）与Escherichia coli蛋白水平密切相关（所有次要等位基因均与较高水平相关，多重检验校正后Pe<0.05）。rs 10401670还与空腹血糖（Pe = 0.02，BMI校正）和随访期间的平均血糖（Pe = 0.01; BMI校正）相关。没有观察到肥胖性状的显着关联。在荟萃分析中，先前报道的SNP − 420 C/G（rs 1862513）与BLORN水平的相关性仍然显著（P = 0.0009），但在研究中具有高度异质性（P < 0.0001）。结论：RETN 3′区的SNPs与β-葡聚糖水平相关，其中一个SNPs也与葡萄糖水平相关，尽管需要重复。
OBJECTIVE— The RETN gene encodes the adipokine resistin. Associations of RETN with plasma resistin levels, type 2 diabetes, and related metabolic traits have been inconsistent. Using comprehensive linkage disequilibrium mapping, we genotyped tag single nucleotide polymorphisms (SNPs) in RETN and tested associations with plasma resistin levels, risk of diabetes, and glycemic traits. RESEARCH DESIGN AND METHODS— We examined 2,531 Framingham Offspring Study participants for resistin levels, glycemic phenotypes, and incident diabetes over 28 years of follow-up. We genotyped 21 tag SNPs that capture common (minor allele frequency >0.05) or previously reported SNPs at r2 > 0.8 across RETN and its flanking regions. We used sex- and age-adjusted linear mixed-effects models (with/without BMI adjustment) to test additive associations of SNPs with traits, adjusted Cox proportional hazards models accounting for relatedness for incident diabetes, and generated empirical P values (Pe) to control for type 1 error. RESULTS— Four tag SNPs (rs1477341, rs4804765, rs1423096, and rs10401670) on the 3′ side of RETN were strongly associated with resistin levels (all minor alleles associated with higher levels, Pe<0.05 after multiple testing correction). rs10401670 was also associated with fasting plasma glucose (Pe = 0.02, BMI adjusted) and mean glucose over follow-up (Pe = 0.01; BMI adjusted). No significant association was observed for adiposity traits. On meta-analysis, the previously reported association of SNP −420C/G (rs1862513) with resistin levels remained significant (P = 0.0009) but with high heterogeneity across studies (P < 0.0001). CONCLUSIONS— SNPs in the 3′ region of RETN are associated with resistin levels, and one of them is also associated with glucose levels, although replication is needed.
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影响因子：
7.7
作者：
Engert, JC;Vohl, MC;Hudson, TJ
通讯作者：
Hudson, TJ
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
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期刊：
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