Stern M P, Duggirala R, Mitchell B D, Reinhart L J, Shivakumar S, Shipman P A, Uresandi O C, Benavides E, Blangero J, O'Connell P
Department of Medicine, University of Texas Health Science Center, San Antonio 78284, USA.
Genome Res. 1996 Aug;6(8):724-34. doi: 10.1101/gr.6.8.724.
The genetic factors involved in type II diabetes are still unknown. To address this problem, we are creating a 10 to 15 cM genetic map on 444 individuals from 32 Mexican American families ascertained on a type II diabetic proband. Using highly polymorphic microsatellite markers and a multipoint variance components method, we found evidence for linkage of plasma glucose concentration 2 hr after oral glucose administration to two regions on chromosome 11: beta-hemoglobin (HBB) and markers D11S899/D11S1324 near the sulfonylurea receptor (SUR) gene. Iod scores at these two loci were 2.77 and 3.37, respectively. The SUR gene region accounted for 44.7% of the phenotypic variance. Evidence for linkage to fasting glucose concentration was also observed for two loci on chromosome 6, one of which is identical to a proposed susceptibility locus for type I diabetes (D6S290). When diabetics were excluded from the analyses, all Iod scores became zero, suggesting that the observed linkages were with the trait diabetes rather than with normal variation in glucose levels. Results were similar whether all diabetics were included in the analyses or only those who were not under treatment with oral antidiabetic agents or insulin.
II型糖尿病所涉及的遗传因素仍然未知。为了解决这个问题，我们正在为32个墨西哥裔美国家庭的444名个体构建一个10至15厘摩的遗传图谱，这些家庭是通过II型糖尿病先证者确定的。使用高度多态的微卫星标记和多点方差成分法，我们发现口服葡萄糖后2小时血浆葡萄糖浓度与11号染色体上的两个区域存在连锁证据：β-血红蛋白（HBB）以及磺脲类受体（SUR）基因附近的标记D11S899/D11S1324。这两个位点的lod分数分别为2.77和3.37。SUR基因区域占表型变异的44.7%。在6号染色体上的两个位点也观察到与空腹血糖浓度连锁的证据，其中一个与I型糖尿病的一个拟议易感位点（D6S290）相同。当糖尿病患者被排除在分析之外时，所有lod分数都变为零，这表明观察到的连锁是与糖尿病性状相关，而不是与血糖水平的正常变异相关。无论所有糖尿病患者都纳入分析，还是仅纳入那些未接受口服降糖药或胰岛素治疗的患者，结果都是相似的。
