KCNQ4:: A gene for age-related hearing impairment?
KCNQ4:: A gene for age-related hearing impairment?
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DOI：
10.1002/humu.20375
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发表时间：
2006-10-01
期刊：
影响因子：
3.9
通讯作者：
Van Camp, G.
中科院分区：
文献类型：
--
作者：
Van Eyken, E.;Van Laer, L.;Van Camp, G.
听觉相关性听力障碍（ARHI）是老年人中最常见的感觉障碍。它是一种复杂的疾病，受遗传和环境因素的影响。在两个独立的高加索人群中检测了候选易感基因KCNQ 4的SNP。研究了两个数量性状基因座（QTL）值：Z（高）和Z（低），分别测量高频和低频听力损失。在第一群体中，对分布在KCNQ 4上的23种基因分型的SNP的统计分析导致Z（高）-SNP 9（NT_004511：g.11244177A > T）和SNP 15（NT_004511：g.11257005C > T，NP_004691：p. Ala 259 Ala）的两种SNP的显著p值，以及Z（低）-SNP 12（NT_004511：g.11249550A > T）的一种SNP的显著p值。随后在显著SNP周围的34-kb区域中确定KCNQ 4的连锁不平衡（LD）结构，从而产生三个LD块。LD-区块I含有SNP 9并且覆盖5 kb的区域，LD-区块2测量5 kb并且围绕SNP 13（NT_004511：g.11253513A > G）至SNP 18（NT_004511：g.11257509G > A; NP_004691：p.Thr293Thr），并且LD，区块3跨越7 kb。随后在第二群体中对区块1和2的5个tag-SNP以及2个额外的SNP进行基因分型。同样，几个SNP与ARHI正相关：一个SNP（SNP 18）与高频率相关，三个SNP（SNP 9，SNP 12和SNP 18）与低频率相关，尽管只有一个SNP（SNP 12）在两个人群中产生显著的p值。然而，两个群体的相关SNP都位于KCNQ 4基因中间的相同13-kb区域。
Age-related hearing impairment (ARHI) is the most common sensory impairment among the elderly. It is a complex disorder influenced by genetic as well as environmental factors. SNPs in a candidate susceptibility gene, KCNQ4, were examined in two independent Caucasian populations. Two quantitative trait locus (QTL) values were investigated: Z(high) and Z(low), a measure of high and respectively low frequency hearing loss. In the first population, the statistical analysis of 23 genotyped SNPs spread across KCNQ4 resulted in significant p,values for two SNPs for Z(high)-SNP9 (NT_004511:g.11244177A > T) and SNP15 (NT_004511: g.11257005C > T, NP_004691:p.Ala259Ala), and one SNP for Z(low)-SNP12 (NT_004511: g.11249550A > T). The linkage disequilibrium (LD) structure of KCNQ4 was subsequently determined in a 34-kb region surrounding the significant SNP's, resulting in three LD-blocks. LD-block I contains SNP9 and covers an area of 5 kb, LD-block 2 measures 5 kb and surrounds SNP13 (NT_004511:g.11253513A > G) to SNP18 (NT_004511:g.11257509G > A; NP_004691:p.Thr293Thr), and LD,block 3 spans 7 kb. Five tag-SNPs of block 1 and 2, and 2 extra SNPs were subsequently genotyped in the second population. Again, several SNPs were positively associated with ARHI: one SNP (SNP18) for the high frequencies and three SNPs (SNP9, SNP12, and SNP18) for the low frequencies, although only a single SNP (SNP12) resulted in significant p-values in both populations. Nevertheless, the associated SNP's of both populations were all located in the same 13-kb region in the middle of the KCNQ4 gene.