在 19q13 染色体区域内采用高密度 SNP 基因分型方法，鉴定出 CNOT3 多态性与强直性脊柱炎的关联。

A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis.

机构信息

Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.

出版信息

Ann Rheum Dis. 2012 May;71(5):714-7. doi: 10.1136/annrheumdis-2011-200661. Epub 2012 Jan 31.

DOI:10.1136/annrheumdis-2011-200661

PMID:22294640

Abstract

OBJECTIVE

To identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations.

METHODS

High-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive.

RESULTS

Two markers in two different genes (CNOT3 and LAIR2) showed significant association (p<10(-3)) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19: 59347459-59356564, p=2.43 × 10(-4) to 6.54 × 10(-4)). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73 × 10(-6)). One SNP, located downstream of KIR3DL1, was detected which, tested in combination with HLA-Bw4I80, was associated with AS.

CONCLUSION

A novel significant association was detected between SNP rs1055234 and AS susceptibility.

摘要

目的

鉴定人类白细胞抗原（HLA）-B27 阳性人群中与强直性脊柱炎（AS）相关的 19q13 染色体区域的基因组变异。

方法

对 249 例 AS 患者和 302 例健康对照者进行了 1536 个单核苷酸多态性（SNP）的高通量基因分型。通过对另外两个包含 412 例病例/301 例对照和 144 例病例/203 例对照的队列中的 4 个 SNP 进行基因分型，验证了部分鉴定出的关联。所有选择的个体（病例和对照）均为 HLA-B27 阳性。

结果

两个不同基因（CNOT3 和 LAIR2）中的两个标记与 AS 显著相关（p<10(-3)）。此外，滑动窗口分析显示，在 CNOT3 周围区域的相邻 SNP 组存在关联（Chr19：59347459-59356564，p=2.43×10(-4) 至 6.54×10(-4)）。通过对位于 LAIR2 和 CNOT3 基因附近区域的四个 SNP（rs1055234、rs8111398、rs2287828 和 rs4591276）进行基因分型，在另外两个队列中验证了这些关联。CNOT3 多态性（rs1055234）与 AS 仍存在关联（合并 p=9.73×10(-6)）。检测到一个 SNP，位于 KIR3DL1 下游，与 HLA-Bw4I80 联合检测时与 AS 相关。