An autosomal genome-wide scan for loci linked to pre-diabetic phenotypes in nondiabetic Chinese subjects from the Stanford Asia-Pacific program of hypertension and insulin resistance family study
An autosomal genome-wide scan for loci linked to pre-diabetic phenotypes in nondiabetic Chinese subjects from the Stanford Asia-Pacific program of hypertension and insulin resistance family study
复制标题
DOI：
10.2337/diabetes.54.4.1200
复制
发表时间：
2005-04-01
期刊：
影响因子：
7.7
通讯作者：
Hsiung, CA
中科院分区：
文献类型：
--
作者：
Chiu, YF;Chuang, LM;Hsiung, CA
2 型糖尿病是一种复杂的疾病，涉及遗传和环境因素。胰岛素分泌和胰岛素作用的异常通常先于 2 型糖尿病的发展，并且可以作为遗传图谱的良好定量测量。因此，我们进行了常染色体基因组搜索，以定位来自 411 个核心家族的 1,365 名非糖尿病中国受试者中与这些性状相关的数量性状基因座 (QTL)。使用方差分量方法在多点连锁分析中分析这些对数转换数量性状的残差。空腹胰岛素最显着的 QTL（与胰岛素抵抗稳态模型评估的 QTL 一致）位于 20 号染色体上 37 cM，调整年龄、性别、BMI、抗高血压药物、招募中心和环境因素后，最大经验对数优势 (LOD) 得分为 3.01（经验 P = 0.00006）。在同一区域，空腹血糖 QTL 位于 51 cM，经验 LOD 评分为 2.03（经验 P = 0.0012）。对于不同的糖尿病相关性状，还有其他最大经验 LOD 得分 >= 1.29 的位点位于染色体 1q、2p、5q、7p、9q、10p、14q、18q 和 19q 上。这些基因座可能含有独立或通过这些区域内基因的相互作用调节葡萄糖稳态的基因。
Type 2 diabetes is a complex disease involving both genetic and environmental components. Abnormalities in insulin secretion and insulin action usually precede the development of type 2 diabetes and can serve as good quantitative measures for genetic mapping. We therefore undertook an autosomal genomic search to locate the quantitative trait locus (QTL) linked to these traits in 1,365 nondiabetic Chinese subjects from 411 nuclear families. Residuals of these log-transformed quantitative traits were analyzed in multipoint linkage analysis using a variance-components approach. The most significant QTL for fasting insulin, which coincides with the QTL for homeostasis model assessment of insulin resistance, was located at 37 cM on chromosome 20, with a maximum empirical logarithm of odds (LOD) score of 3.01 (empirical P = 0.00006) when adjusted for age, sex, BMI, antihypertensive medications, recruitment centers, and environmental factors. In the same region, a QTL for fasting glucose was identified at 51 cM, with an empirical LOD score of 2.03 (empirical P = 0.0012). There were other loci with maximum empirical LOD scores >= 1.29 located on chromosomes 1q, 2p, 5q, 7p, 9q, 10p, 14q, 18q, and 19q for different diabetes-related traits. These loci may harbor genes that regulate glucose homeostasis either independently or via interactions of the genes within these regions.