miR-146aおよびIRAK1遺伝子多型と強直性脊椎炎との相関

Correlations of miR-146a and IRAK1 gene polymorphisms with ankylosing spondylitis.

• L Wang
• H Zhang
• N-L Hou

抄録

目的:

本研究の目的は、マイクロリボ核酸（miR）-146aおよびインターロイキン1受容体関連キナーゼ1（IRAK1）遺伝子多型と強直性脊椎炎との相関を探ることであった。

OBJECTIVE: The aim of this study was to explore the correlations of micro ribonucleic acid (miR)-146a and interleukin 1 receptor associated kinase 1 (IRAK1) gene polymorphisms with ankylosing spondylitis.

患者と方法:

当院の強直性脊椎炎患者 200 例を疾患群に登録した．強直性脊椎炎の診断は、1984年のNew York Revised Criteria for Ankylosing Spondylitisに準拠した。一方、健常者200名を対照群とした。疾患群と対照群の患者から末梢血を採取した。その後、miR-146aのrs2910164とrs7702165の多型領域、IRAK1のrs763737とrs3027898の多型領域をポリメラーゼ連鎖反応（PCR）で増幅した。これらの多型は、患者の遺伝子発現と臨床データに基づいて配列解析を行った。

PATIENTS AND METHODS: A total of 200 patients with ankylosing spondylitis in our hospital were enrolled in the disease group. The diagnosis of ankylosing spondylitis was in accordance with the 1984 New York Revised Criteria for Ankylosing Spondylitis. Meanwhile, 200 healthy people were taken as the control group. Peripheral blood was collected from patients in both disease group and control group. Subsequently, polymorphic regions of rs2910164 and rs7702165 in miR-146a and those of rs763737 and rs3027898 in IRAK1 were amplified by polymerase chain reaction (PCR). The polymorphisms were analyzed by sequencing based on gene expression and clinical data of patients.

結果:

疾患群のmiR-146a rs7702165(p=0.008)とIRAK1 rs3027898(p=0.004)の対立遺伝子分布は対照群と有意に異なっていた。また、miR-146a rs7702165の対立遺伝子T頻度とIRAK1 rs3027898の対立遺伝子A頻度は、疾患群で相対的に高かった。また、miR-146a rs2910164（p=0.032）、rs7702165（p=0.000）、IRAK1 rs3027898（p=0.001）の遺伝子型分布には、疾患群と対照群で統計学的に有意な差が認められた。また、miR-146a rs7702165の遺伝子型CGとTTの頻度、IRAK1 rs3027898の遺伝子型AAの頻度は、疾患群の方が高かった。また、IRAK1 rs3027898の優性モデル（p=0.011）とmiR-146a rs7702165の劣性モデル（p=0.015）の分布は、疾患群と対照群で顕著な差が認められた。IRAK1 rs3027898の優性モデルにおけるCC+CAの頻度と、miR-146a rs7702165の劣性モデルにおけるTG+GGの頻度は、疾患群では対照群に比べて低かった。また、miR-146a rs2910164およびrs7702165のハプロタイプCG分布(p<0.043)、IRAK1 rs763737およびrs3027898のハプロタイプGA分布(p=0.035)は、疾患群では対照群と比較して有意な差を示した。miR-146a rs2910164の遺伝子型は、miR-146a（p=0.024）とIRAK1（p=0.002）の発現に相関があることがわかった。同様に、IRAK1遺伝子多型 rs763737はIRAK1の発現と関連し（p=0.023）、さらに、miR-146a遺伝子多型 rs7702165はヒト白血球抗原B27（HLA-B27）のレベルと関連し（p<0.05）、ジェノタイプGGの患者はHLA-B27のレベルが低いことがわかった。また、IRAK1遺伝子多型 rs3027898は患者のC反応性蛋白（CRP）値と相関があり（p<0.05）、遺伝子型CCの患者ではCRP値が相対的に高いことがわかった。

RESULTS: The allele distribution of miR-146a rs7702165 (p=0.008) and that of IRAK1 rs3027898 (p=0.004) in disease group were significantly different from those in control group. Besides, the allele T frequency of miR-146a rs7702165 and the allele A frequency of IRAK1 rs3027898 were relatively higher in disease group. Statistically significant differences in the genotype distribution of miR-146a rs2910164 (p=0.032) and rs7702165 (p=0.000) and that of IRAK1 rs3027898 (p=0.001) were observed between disease group and control group. In addition, the frequencies of genotypes CG and TT of miR-146a rs7702165 and the frequency of genotype AA of IRAK1 rs3027898 were higher in disease group. Moreover, the distribution in the dominant model of IRAK1 rs3027898 (p=0.011) and that in the recessive model of miR-146a rs7702165 (p=0.015) showed remarkable differences between disease group and control group. The frequency of CC+CA in the dominant model of IRAK1 rs3027898 and that of TG+GG in the recessive model of miR-146a rs7702165 in disease group were lower than those in control group. Additionally, the haplotype CG distribution of miR-146a rs2910164 and rs7702165 (p<0.043) and the haplotype GA distribution of IRAK1 rs763737 and rs3027898 (p=0.035) in disease group displayed significant differences compared with those in control group. It was discovered that the genotype of miR-146a rs2910164 was correlated with the expressions of miR-146a (p=0.024) and IRAK1 (p=0.002). Similarly, IRAK1 gene polymorphism rs763737 was related to the expression of IRAK1 (p=0.023), Furthermore, miR-146a gene polymorphism rs7702165 was associated with the level of human leukocyte antigen B27 (HLA-B27) (p<0.05), and patients with genotype GG exhibited a lower level of HLA-B27. In addition, it was found that IRAK1 gene polymorphism rs3027898 was correlated with the C-reactive protein (CRP) level of patients (p<0.05), and CRP level was relatively high in patients with genotype CC.

結論:

miR-146aおよびIRAK1遺伝子多型は強直性脊椎炎と顕著に関連している。

CONCLUSIONS: MiR-146a and IRAK1 gene polymorphisms are prominently associated with ankylosing spondylitis.