Shtir Corina, Nagakawa I Sharon, Duren William L, Conneely Karen N, Scott Laura J, Silander Kaisa, Valle Timo T, Tuomilehto Jaakko, Buchanan Thomas A, Bergman Richard N, Collins Francis S, Boehnke Michael, Watanabe Richard M
Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA 90089, USA.
Hum Hered. 2007;63(1):17-25. doi: 10.1159/000097927. Epub 2006 Dec 14.
The purpose of this study was to examine carefully heterogeneity underlying evidence for linkage to type 2 diabetes (T2DM) on chromosome 6q from two sets of FUSION families.
Ordered subsets analysis (OSA) was performed on two sets of FUSION families. For OSA results showing significant improvement in evidence for linkage, T2DM-related phenotypes were compared between individuals with T2DM within the subset versus the complement.
OSA analysis revealed 105 families with the highest average HDL to total cholesterol ratio (HDL ratio) that had strongly increased evidence for linkage (MLS = 7.91 at 78.0 cM; uncorrected p = 0.00002). Subjects with T2DM within this subset were significantly leaner, had lower fasting glucose, insulin, and C-peptide, and more favorable cardiovascular risk profile compared to the complement set of subjects with T2DM. OSA also revealed 33 families with the lowest average fasting insulin that had increased evidence for linkage at a second locus (MLS = 3.45 at 128 cM; uncorrected p = 0.017) coincident with quantitative trait locus linkage analysis results for fasting and 2-hour insulin in subjects without T2DM.
These results suggest two diabetes susceptibility loci on chromosome 6q that may affect subsets of individuals with a milder form of T2DM.
本研究旨在仔细检验来自两组FUSION家族的6号染色体q臂上与2型糖尿病（T2DM）连锁的证据背后的异质性。
对两组FUSION家族进行有序子集分析（OSA）。对于显示连锁证据有显著改善的OSA结果，比较子集中患有T2DM的个体与其余个体之间的T2DM相关表型。
OSA分析显示，105个家族的平均高密度脂蛋白与总胆固醇比值（HDL比值）最高，其连锁证据显著增加（在78.0厘摩处MLS = 7.91；未校正p = 0.00002）。与其余患有T2DM的受试者相比，该子集中患有T2DM的受试者明显更瘦，空腹血糖、胰岛素和C肽水平更低，心血管风险状况更有利。OSA还显示，33个家族的平均空腹胰岛素水平最低，在第二个位点有增加的连锁证据（在128厘摩处MLS = 3.45；未校正p = 0.017），这与非T2DM受试者空腹和2小时胰岛素的数量性状位点连锁分析结果一致。
这些结果提示6号染色体q臂上有两个糖尿病易感位点，可能影响症状较轻的T2DM个体亚组。
