Kovac Ilija P, Havlik Richard J, Foley Daniel, Peila Rita, Hernandez Dena, Wavrant-De Vrièze Fabienne, Singleton Andrew, Egan Josephine, Taub Dennis, Rodriguez Beatriz, Masaki Kamal, Curb J David, Fujimoto Wilfred Y, Wilson Alexander F
Department of Psychiatry, McGill University, Alan Memorial Institute, R&T Building, 1033 Pine Avenue West, Montreal H3A 1A1, Quebec, Canada.
Diabetes. 2007 Feb;56(2):537-40. doi: 10.2337/db06-0443.
Type 2 diabetes is a common disorder associated with obesity. Lower plasma levels of adiponectin were associated with type 2 diabetes. Candidate regions on chromosomes 1 ( approximately 70 cM) and 14 ( approximately 30 cM) were evaluated for replication of suggestive linkage results for type 2 diabetes/impaired glucose homeostasis in an independent sample of Japanese Americans. Replication of independent linkage evidence for serum levels of adiponectin on chromosome 14 was also evaluated. We investigated 529 subjects from 175 sibships who were originally part of the Honolulu Heart Program. Analyses included nonparametric linkage and association using SAGE (Statistical Analysis for Genetic Epidemiology) and FBAT (family-based test of association) programs and Monte Carlo simulation of Fisher's exact test in SAS. For type 2 diabetes/impaired glucose metabolism, nominal linkage evidence (P < 0.02) followed-up by genotypic association (P = 0.016) was found with marker D14S297 at 31.8 cM; linkage analyses using only diabetes phenotype were also nominally significant at this marker (P < 0.02). Nominal evidence for genotypic association to adiponectin serum level phenotype (P = 0.04) was found with the marker D14S1032 at 23.2 cM. The present study was limited by relatively small sample size. Nevertheless, these results corroborate earlier studies, suggesting that further research is warranted in the candidate region approximately 30 cM on chromosome 14.
2型糖尿病是一种与肥胖相关的常见疾病。脂联素血浆水平较低与2型糖尿病有关。对1号染色体（约70厘摩）和14号染色体（约30厘摩）上的候选区域进行评估，以在一个日裔美国人独立样本中重复2型糖尿病/葡萄糖稳态受损的提示性连锁结果。还评估了14号染色体上脂联素血清水平独立连锁证据的重复性。我们调查了来自175个同胞家庭的529名受试者，他们最初是檀香山心脏项目的一部分。分析包括使用SAGE（遗传流行病学统计分析）和FBAT（基于家系的关联检验）程序进行非参数连锁和关联分析，以及在SAS中对Fisher精确检验进行蒙特卡罗模拟。对于2型糖尿病/葡萄糖代谢受损，在31.8厘摩处的标记D14S297发现了名义连锁证据（P < 0.02），随后进行基因型关联分析（P = 0.016）；仅使用糖尿病表型的连锁分析在该标记处也具有名义显著性（P < 0.02）。在23.2厘摩处的标记D14S1032发现了与脂联素血清水平表型的基因型关联的名义证据（P = 0.04）。本研究受到样本量相对较小的限制。尽管如此，这些结果证实了早期研究，表明对14号染色体上约30厘摩的候选区域进行进一步研究是有必要的。
