Kaimen-Maciel Damacio Ramón, Reiche Edna Maria Vissoci, Brum Souza Doralina Guimarães, Frota Comini Elisabeth Regina, Bobroff Flavio, Morimoto Helena Kaminami, Ehara Watanabe Maria Angélica, Carvalho De Oliveira Jaqueline, Matsuo Tiemi, Lopes Josiane, Donadi Eduardo Antonio
Department of Clinical Medicine, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.
Int J Mol Med. 2007 Sep;20(3):337-44.
The CCR5 chemokine receptor has been implicated in the pathogenesis of multiple sclerosis (MS). This research was carried out to investigate the association between the CCR5-Delta32 deletion in 124 patients with MS from Southern Brazil. Ninety-eight (79.0%) patients presented with relapsing-remitting MS (RR-MS), 17 (13.7%) secondary progressive MS (SP-MS), 8 (6.5%) primary progressive MS (PP-MS) and one (0.8%) clinically isolated syndrome (CIS). The control group consisted of 127 healthy blood donors from the same geographic region. The disease severity was assessed clinically using the Expanded Disability Status Scale (EDSS). Genomic DNA was extracted from peripheral blood cells and the genetic polymorphism was evaluated by polymerase chain reaction. Of the MS patients, 85 (68.5%) were females (p=0.0093). The CCR5-Delta32 frequency among the controls was 5.5%, and did not differ from that observed among the MS patients (4.8%) (p=0.7337). The mean (+/-SD) age at disease onset among the carriers and non-carriers of the CCR5-Delta32 allele was 31.7 (+/-11.1) and 36.6 (+/-12.0) years, respectively (p=0.1312). The duration (+/-SD) of the disease was 11.2 (+/-12.9) and 7.7 (+/- 5.6) years among the CCR5-Delta32 heterozygous, and CCR5 wild type, respectively (p=0.396). The mean (+/-SD) EDSS among the MS patients carriers and non-carriers of the CCR5-Delta32 allele was 2.4+/-1.2 and 2.67+/-2.2, respectively (p=0.9796). The MRI findings in MS patients with the CCR5-Delta32 genotype exhibited lower positive gadolinium enhancing-imaging (p=0.0013) and lower brain atrophy (p=0.1333) than MS patients with the CCR5 wild-type genotype. Despite that the differences were not significant, the results suggested that the disease onset and progression to disability may be prolonged in MS carriers of CCR5-Delta32, and CCR5-Delta32 could be considered a favorable prognostic biomarker of MS. Further studies comprising larger numbers of individuals carrying non-wild-type haplotypes are needed to determine CCR5-Delta32 involvement in the specific process of MS pathology and pathogenesis.
CCR5趋化因子受体与多发性硬化症（MS）的发病机制有关。本研究旨在调查巴西南部124例MS患者中CCR5-Delta32缺失的相关性。98例（79.0%）患者表现为复发缓解型MS（RR-MS），17例（13.7%）为继发进展型MS（SP-MS），8例（6.5%）为原发进展型MS（PP-MS），1例（0.8%）为临床孤立综合征（CIS）。对照组由来自同一地理区域的127名健康献血者组成。使用扩展残疾状态量表（EDSS）对疾病严重程度进行临床评估。从外周血细胞中提取基因组DNA，并通过聚合酶链反应评估基因多态性。在MS患者中，85例（68.5%）为女性（p=0.0093）。对照组中CCR5-Delta32的频率为5.5%，与MS患者中观察到的频率（4.8%）无差异（p=0.7337）。CCR5-Delta32等位基因携带者和非携带者的疾病发病平均年龄（±标准差）分别为31.7（±11.1）岁和36.6（±12.0）岁（p=0.1312）。CCR5-Delta32杂合子和CCR5野生型患者的疾病持续时间（±标准差）分别为11.2（±12.9）年和7.7（±5.6）年（p=0.396）。CCR5-Delta32等位基因携带者和非携带者的MS患者的平均（±标准差）EDSS分别为2.4±1.2和2.67±2.2（p=0.9796）。与CCR5野生型基因型的MS患者相比，CCR5-Delta32基因型的MS患者的MRI结果显示钆增强成像阳性率较低（p=0.0013），脑萎缩程度较低（p=0.1333）。尽管差异不显著，但结果表明CCR5-Delta32的MS携带者的疾病发病和进展至残疾可能会延长，CCR5-Delta32可被视为MS的一个有利预后生物标志物。需要进一步开展包含更多携带非野生型单倍型个体的研究，以确定CCR（5-Delta32）在MS病理和发病机制的特定过程中的作用。
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