Chistiakov Dimitry A, Chernisheva Ana, Savost'anov Kirill V, Turakulov Rustam I, Kuraeva Tamara L, Dedov Ivan I, Nosikov Valery V
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, PO Box 670529, 231 Albert Sabin Way, Cincinnati, OH 45267-0529, USA.
Croat Med J. 2005 Aug;46(4):670-7.
To evaluate whether the T1D susceptibility locus on chromosome 16q contributes to the genetic susceptibility to T1D in Russian patients.
Thirteen microsatellite markers, spanning a 47-centimorgan genomic region on 16q22-q24 were evaluated for linkage to T1D in 98 Russian multiplex families. Multipoint logarithm of odds (LOD) ratio (MLS) and nonparametric LOD (NPL) values were computed for each marker, using GENEHUNTER 2.1 software. Four microsatellites (D16S422, D16S504, D16S3037, and D16S3098) and 6 biallelic markers in 2 positional candidate genes, ICSBP1 and NQO1, were additionally tested for association with T1D in 114 simplex families, using transmission disequilibrium test (TDT).
A peak of linkage (MLS=1.35, NPL=0.91) was shown for marker D16S750, but this was not significant (P=0.18). The subsequent linkage analysis in the subset of 46 multiplex families carrying a common risk HLA-DR4 haplotype increased peak MLS and NPL values to 1.77 and 1.22, respectively, but showed no significant linkage (P=0.11) to T1D in the 16q22-q24 genomic region. TDT analysis failed to find significant association between these markers and disease, even after the conditioning for the predisposing HLA-DR4 haplotype.
Our results did not support the evidence for the susceptibility locus to T1D on chromosome 16q22-24 in the Russian family data set. The lack of association could reflect genetic heterogeneity of type 1 diabetes in diverse ethnic groups.
评估16号染色体上的1型糖尿病（T1D）易感基因座是否对俄罗斯患者T1D的遗传易感性有影响。
在98个俄罗斯多基因家族中，对跨越16q22 - q24上47厘摩基因组区域的13个微卫星标记进行T1D连锁评估。使用GENEHUNTER 2.1软件计算每个标记的多点优势对数（LOD）比（MLS）和非参数LOD（NPL）值。另外，在114个单基因家族中，使用传递不平衡检验（TDT）对2个位置候选基因ICSBP1和NQO1中的4个微卫星（D16S422、D16S504、D16S3037和D16S3098）以及6个双等位基因标记与T1D的关联性进行检测。
标记D16S750显示出连锁峰值（MLS = 1.35，NPL = 0.91），但不显著（P = 0.18）。在携带常见风险HLA - DR4单倍型的46个多基因家族子集中进行的后续连锁分析，使峰值MLS和NPL值分别增加到1.77和1.22，但在16q22 - q24基因组区域与T1D无显著连锁（P = 0.11）。即使在对易感HLA - DR4单倍型进行条件设定后，TDT分析也未发现这些标记与疾病之间存在显著关联。
我们的结果不支持俄罗斯家族数据集中16q22 - 24染色体上存在T1D易感基因座的证据。缺乏关联性可能反映了不同种族中1型糖尿病的遗传异质性。
