Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study
Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study
复制标题
DOI：
10.1016/j.metabol.2005.05.007
复制
发表时间：
2005-11-01
影响因子：
9.8
通讯作者：
Fox, CS
中科院分区：
文献类型：
--
作者：
Yang, Q;Guo, CY;Fox, CS
血清尿酸水平与高血压、心血管疾病和肾脏疾病有关。尿酸已被证明是可遗传的，然而，全基因组连锁分析尚未报道。采用1971年和1979年前后的第一次和第二次检查中获得的两次血清尿酸测量值的平均值，对1258名心脏病研究受试者进行了全基因组多点方差分量连锁分析，其中401个标记的间隔约为10厘摩（cM）。完全校正模型中的协变量包括性别、年龄、体重指数（BMI）、血清肌酐、饮酒量、糖尿病、利尿剂治疗和甘油三酯。为了研究尿酸与可能具有遗传成分的协变量之间可能的多效性效应，在尿酸连锁区域进行了尿酸与BMI、甘油三酯和葡萄糖的双变量连锁分析。尿酸的遗传度为0.63。年龄-性别校正尿酸的最高多点比值对数（LOD）评分为15号染色体上50 cM处的3.3，但在多变量校正后降至1.5。对于多变量校正尿酸，在2号染色体（LOD评分1.1，4 cM）和8号染色体（LOD评分1.7，6 cM）上观察到连锁的其他证据。多效性效应仅在尿酸和葡萄糖与BMI之间发现，分别在8号和15号染色体的连锁位置。我们已经确定了几个新的位点与尿酸。我们发现尿酸和BNI和葡萄糖之间可能存在多效性效应。需要进一步研究以确定参与尿酸代谢的基因及其在高血压、心血管疾病和肾脏疾病中的作用。(c)2005年爱思唯尔公司All rights reserved.
Serum uric acid levels are associated with hypertension, cardiovascular disease, and renal disease. Uric acid has been shown to be heritable; however, genome-wide linkage analyses have not been reported. Genome-wide multipoint variance components linkage analyses with 401 markers spaced at approximately 10 centimorgan (cM) were conducted on 1258 subjects of the Framingham Heart Study, using the average of two serum uric acid measurements obtained in examinations I and 2 around 1971 and 1979. Covariates in fully adjusted model included sex, age, body mass index (BMI), serum creatinine, alcohol consumption, diabetes, diuretic treatment, and triglycerides. To investigate possible pleiotropic effects between uric acid and covariates that may have a genetic component, bivariate linkage analyses of uric acid with BMI, triglycerides, and glucose were conducted at the uric acid linkage regions. The heritability of uric acid was 0.63. The highest multipoint log-of-the-odds (LOD) score was 3.3 at 50 cM on chromosome 15 for age-sex-adjusted uric acid, but decreased to 1.5 after multivariable adjustment. Additional evidence of linkage was seen on chromosomes 2 (LOD score 1.1 at 4 cM) and 8 (LOD score 1.7 at 6 cM) for multivariable-adjusted uric acid. Pleiotropic effects were only found between uric acid and glucose and BMI at chromosomes 8 and 15 linkage locations, respectively. We have identified several novel loci linked to uric acid. We found possible pleiotropic effects between uric acid and BNI and glucose. Further research is necessary to identify the genes involved in uric acid metabolism and their roles in hypertension, cardiovascular disease, and renal disease. (c) 2005 Elsevier Inc. All rights reserved.