Mutations in the SLC30A8 gene are not a major cause of MODY or other forms of early-onset, autosomal dominant type 2 diabetes.
Mutations in the SLC30A8 gene are not a major cause of MODY or other forms of early-onset, autosomal dominant type 2 diabetes.
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SLC30A8 基因突变并不是 MODY 或其他形式的早发性常染色体显性 2 型糖尿病的主要原因。
DOI：
10.1007/s00125-007-0777-y
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发表时间：
2007
期刊：
影响因子：
8.2
通讯作者：
Doria,A
中科院分区：
文献类型：
--
作者：
Borowiec,M;Thompson,R;Powers,C;Xu,R;Dickey,T;Doria,A
致编辑：MODY是一种相对罕见的家族性糖尿病，其特点是发病年龄小，常染色体显性遗传。具有多个受影响成员的大家族的可用性促进了这种综合征的遗传研究，这导致了六种不同的MODY基因的鉴定[1]。一些报告表明，其他MODY基因存在除了那些确定的日期[1，2]。在英国，大约15%的MODY病例似乎不是由已知的MODY基因突变引起的[2]。如果使用更广泛的疾病定义，考虑到MODY通常在传统的25岁年龄限制之后被诊断出来，那么未考虑的MODY比例甚至更高[1]。最近发现的导致2型糖尿病多因素形式的常见多态性[3-6]提出了一种假设，即相同基因中更严重但不太常见的突变可能是不明原因的MODY病例的原因。证明这一假设将为这些基因在糖尿病中的作用提供进一步的支持，并将提供有用的单基因模型来研究这些基因功能障碍导致高血糖症的机制。这类似于其他基因，如KCNJ 11，PPARG，HNF 4A和GCK，其中突变导致单基因糖尿病，常见的遗传变异与2型糖尿病的易感性增加有关。在最近描述的遗传变异在2型糖尿病易感性中起作用的基因中，编码锌转运蛋白溶质载体家族30成员8（SLC 30 A8）的基因是一个特别令人感兴趣的候选者，因为它几乎只在β细胞中表达，并且该基因中的氨基酸多态性与以相对年轻的发病为特征的2型糖尿病形式相关，leanness [3].虽然先前的全基因组扫描与MODY的连锁没有在SLC 30 A8（8 q24）区域确定相当大的比值对数（LOD）分数[7，8]，但该基因的突变可能在选定的家族中发挥作用。
To the Editor: MODY is a relatively rare type of familial diabetes that is characterised by a young age of onset and an autosomal dominant mode of inheritance. The availability of large families with multiple affected members has facilitated genetic studies of this syndrome and this has led to the identification of six distinct MODY genes [1]. Several reports suggest that other MODY genes exist in addition to those identified to date [1, 2]. In the UK, about 15% of MODY cases do not seem to result from mutations in known MODY genes [2]. The proportion of unaccounted MODY is even higher if one uses a broader definition of the disease, one that takes into account the fact that MODY is often diagnosed after the traditional age limit of 25 years [1]. The recent identification of common polymorphisms contributing to multifactorial forms of type 2 diabetes [3–6] raises the hypothesis that more severe but less common mutations in the same genes may be responsible for unaccounted MODY cases. Proving this hypothesis would provide further support for a role of these genes in diabetes, and would offer useful monogenic models to study the mechanisms through which dysfunction of these genes cause hyperglycaemia. This would be analogous to other genes such as KCNJ11, PPARG, HNF4A, and GCK, in which mutations cause monogenic diabetes, and common genetic variation is associated with increased susceptibility to type 2 diabetes. Of the recently described genes in which genetic variation plays a role in susceptibility to type 2 diabetes, the gene encoding the zinc transporter solute carrier family 30 member 8 (SLC30A8) is an especially interesting candidate because of its almost exclusive expression in beta cells and the association of an amino acid polymorphism in this gene with forms of type 2 diabetes characterised by a relatively young onset and leanness [3]. While previous genome-wide scans for linkage with MODY have not identified sizable logarithm of odds (LOD) scores in the region of SLC30A8 (8q24)[7, 8], mutations in this gene might play a role in selected families.