CTLA4基因多态性与俄罗斯人群中的胰岛素依赖型糖尿病相关并存在联系。

CTLA4 gene polymorphisms are associated with, and linked to, insulin-dependent diabetes mellitus in a Russian population.

作者信息

Chistiakov D A, Savost'anov K V, Nosikov V V

机构信息

INSERM U36-College de France, 75231 Paris Cedex 05, France.

出版信息

BMC Genet. 2001;2:6. doi: 10.1186/1471-2156-2-6. Epub 2001 Mar 27.

DOI:10.1186/1471-2156-2-6

PMID:11286636

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC31345/

Abstract

BACKGROUND

The association between the human cytotoxic T lymphocyte-associated antigen-4 (CTLA4) gene and insulin-dependent diabetes mellitus (IDDM) is unclear in populations. We therefore investigated whether the gene conferred susceptibility to IDDM in a Russian population. We studied two polymorphic regions of the CTLA4 gene, the codon 17 dimorphism and the (AT)n microsatellite marker in the 3' untranslated region in 56 discordant sibling pairs and in 33 identical by descent (IBD) affected sibships.

RESULTS

The Alal7 allele of the CTLA4 gene was preferentially transmitted from parents to diabetic offspring (p<0.0001) as shown by the combined transmission/disequlibrium test (TDT) and sib TDT (S-TDT) analysis. A significant difference between diabetic and non-diabetic offspring was also observed for the transmission of alleles 17, 20, and 26 of the dinucleotide microsatellite. Allele 17 was transmitted significantly more frequently to affected offspring than to other children (p=0.0112) whereas alleles 20 and 26 were transmitted preferentially to non-diabetic sibs (p=0.045 and 0.00068 respectively). A nonrandom excess of the Ala17 CTLA4 molecular variant (maximum logarithm of odds score (MLS) of 3.26) and allele 17 of the dinucleotide marker (MLS=3.14) was observed in IBD-affected sibling pairs.

CONCLUSION

The CTLA4 gene is strongly associated with, and linked to IDDM in a Russian population.

摘要

背景

在人群中，人类细胞毒性T淋巴细胞相关抗原4（CTLA4）基因与胰岛素依赖型糖尿病（IDDM）之间的关联尚不清楚。因此，我们调查了该基因是否使俄罗斯人群易患IDDM。我们研究了CTLA4基因的两个多态性区域，即第17密码子二态性和3'非翻译区的（AT）n微卫星标记，研究对象为56对不一致的同胞对以及33对完全相同的受影响同胞对。

结果

通过联合传递/不平衡检验（TDT）和同胞TDT（S-TDT）分析表明，CTLA4基因的Ala17等位基因优先从父母传递给糖尿病后代（p<0.0001）。对于二核苷酸微卫星的17、20和26等位基因的传递，糖尿病和非糖尿病后代之间也观察到显著差异。等位基因17传递给受影响后代的频率明显高于其他孩子（p=0.0112），而等位基因20和26则优先传递给非糖尿病同胞（分别为p=0.045和0.00068）。在受IBD影响的同胞对中观察到Ala17 CTLA4分子变体（最大优势对数评分（MLS）为3.26）和二核苷酸标记的等位基因17（MLS=3.14）存在非随机过量。