Komlósi K, Talián G C, Faragó B, Magyari L, Cserép V, Kovács B, Bene J, Havasi V, Kiss C G, Czirják L, Melegh B
Department of Medical Genetics and Child Development, University of Pécs, Pécs, Hungary.
Clin Exp Rheumatol. 2008 Jan-Feb;26(1):61-6.
In a Japanese study, the C6607T SNP mapping to intron 1 of the SLC22A4 gene encoding the OCTN1 protein was found to be associated with rheumatoid arthritis. Similarly, a G24658C transversion in intron 6 of the gene encoding the RUNX1 transcription factor that regulates OCTN1 and also likely OCTN2 expression was also found to confer susceptibility to the disease.
We investigated the prevalence of these two SNPs by RFLP analysis in a cohort of 209 Hungarian rheumatoid arthritis patients, and 217 healthy controls. Since both the OCTN1 and OCTN2 play a central role in the transmembrane transport of carnitine, we also determined the quantitative serum carnitine ester profile by ESI tandem mass spectrometry.
No statistically significant differences were found comparing the genotype prevalence rates between the patients and the controls for either the SLC22A4 genotypes or for the RUNX1 SNPs. There was no significant difference in the serum carnitine ester profile when the rheumatoid arthritis patients were compared with the controls; furthermore, no significant difference in the carnitine esters could be detected when genotype specific subgroups of the patients and the controls were studied.
Data of the current study do not confirm the universal and population independent susceptibility role of the SLC22A4 C6607T and RUNX1 G24658C variants for rheumatoid arthritis; furthermore, the data presented here show, that there are no significant carnitine-metabolism associated functional consequences of the different genotypes evidenced by the lack of detectable differences in the carnitine ester profiles.
在一项日本研究中，发现位于编码OCTN1蛋白的SLC22A4基因内含子1的C6607T单核苷酸多态性（SNP）与类风湿性关节炎相关。同样，在编码调控OCTN1以及可能还有OCTN2表达的RUNX1转录因子的基因内含子6中发现的G24658C颠换也被发现会使人易患该病。
我们通过限制性片段长度多态性（RFLP）分析，在209名匈牙利类风湿性关节炎患者和217名健康对照者组成的队列中研究了这两种SNP的患病率。由于OCTN1和OCTN2在肉碱的跨膜转运中都起着核心作用，我们还通过电喷雾串联质谱法测定了血清肉碱酯的定量图谱。
在SLC22A4基因型或RUNX1 SNP方面，比较患者和对照者的基因型患病率，未发现统计学上的显著差异。将类风湿性关节炎患者与对照者进行比较时，血清肉碱酯图谱没有显著差异；此外，在研究患者和对照者的基因型特异性亚组时，未检测到肉碱酯有显著差异。
本研究的数据不支持SLC22A4基因的C6607T和RUNX1基因的G24658C变体在类风湿性关节炎中具有普遍且不依赖人群的易感性作用这一观点；此外，此处呈现的数据表明，不同基因型在肉碱代谢方面没有显著的功能后果，这一点可由肉碱酯图谱中未检测到差异得到证明。
