The Research On The Relationships Between Gene Polymorphisms In The 17q11.2-12 CC Chemokine 23 (CCL23), EBV And HHV-6 Type B Infection And Multiple Sclerosis

Background: Multiple sclerosis (MS) is a chronic inflammatory and auto-immune demyelinating human disease in the central nervous system (CNS)with unknown etiology. Epidemiological studies suggest a multifactorial aetiology for MS, implicating a complex interaction between environmental and genetic factors. Environmental factors, such as virus infections, operate on a background of genetic susceptibility in the pathogenesis of MS. Eptein-Barr virus(EBV) and Human herpersviru-6(HHV-6) are two key factors associated with MS. Chemokines are vital to the migration of cells to sites of inflammation, including the CNS, and many of them are implicated in MS pathogenesis. Substantial evidence supports the involvement of CC Chemokines in the pathogenesis of MS. Polymorphisms from CC chemokine genes in the 17qll. 2-12 region has been implicated for association with MS. After searching at NCBI, we found that there are two single-loci (rs854655 and rs1003645) having single nucleotide polymorphisms (SNPs) and heavy population diversity located in 17q11.2-12 CCL23 region in Chinese people. This is coincided with Bugeja's study result. At present we have not found any reports about the relationships between the two loci and MS. Object:1.To investigate the relationships between gene polymorphisms in the17qll. 2-12 CCL23 and MS.2. To investigate the relationships between infection of EBV and HHV-6 typeB and MSMethods:1. Both cases and healthy controls are Henan Han Chinese. From May 2002 to march 2007, 35 MS patients (Clinical definite MS or Laboratory-supported definite MS patient) were selected from outpatients or inpatients in Neurology Department of the First Affiliated Hospital of Zhengzhou University. There were 3 control groups. They were NID group (nervous inflammatory diseases group), NNID group (nervous non-inflammatory diseases group) and healthy control group individually. 22 patients in NID group and 27 patients in NNID group were selected from in-patient Department of Neurology of the First Affiliated Hospital of Zhengzhou University. 35 healthy controls were selected from the healthy donators of the Red Cross Donating Blood Center of Henan Province.2. Peripheral venous blood and serum samples were collected, and the whole genomic DNA was extracted from white blood cells. Our detection was based on ligase detection reaction (LDR)and DNA chip-based genotyping technology to determine the gene polymorphisms of the two single-locuses in CCL23 from all samples. ELISA test was used to examine the anti-EBV EA(IgG , IgM) antibodies from all of the serum samples. Indirect immunofluorescence test was taken to determinate HHV-6 type B(IgG, IgM) antibodies from all of the serum samples and visualization was by using fluorescence microscopy.3. Statistical analysis utilized SPSS 11. 0 software. We used multivariate analysis between groups and Pearson chi-square or Fisher's Exact Test within group to analyze (1)The relationship between the gene polymorphisms of the two single-locuses in CCL23 and MS (2)The relationship between EBV primary infection and MS (3)The relationship between HHV-6 type B infection and MS.Results:1. There were 12 men and 23 women in MS group. Age ranged from 16 to 69 years , and mean age was 35. 59±15. 09 years; There were 16 men and 6 women in NID group. Age ranged from 13 to 65 years, and mean age is 39. 14±14. 82 years; There were 17 men and 10 women in NNID group. Age ranged from 17 to 75 years, and mean age is 49. 78±15.91 years; There were 12 men and 23 women in healthy control group. Age ranged from 18 to 53 years, and mean age is 38.39±7.28 years.2. Two polymorphisms loci located in CCL23 were rs854655 and rsl003645. We didn' t find significant difference in the genotypes frequencies of these two polymorphisms loci by comparing MS group and all three control groups individually (P>0. 05).3. There was no significant difference in the detection rate of anti EBV EA IgG antibody by comparing MS group and three control groups individually (P>0. 05).4. There were significant differences in the detection rates of anti-EBV EA IgM antibody by comparing MS group with NID group or NNID group (P=0. 014;P=0. 027). But there was no significant difference between MS group and healthy control group (P>0. 05).5. We found significant difference in the detection rates of HHV-6 type B IgG antibody by comparing MS group and all three control groups individually(P=0. 007;P=0. 001;P=0.001). 6. There were significant differences in the detection rates of HHV-6 type B IgM antibody by comparing MS group with NNID group or healthy control group (P=0. 013;P=0.01). But there was no significant difference between MS group and NID group(P>0. 05).Conclusion :1. Gene polymorphisms of rs854655 and rsl003645 in CCL23 are probably common in Henan Han Chinese. But our study didn' t indicate any association of gene polymorphisms with MS.2. HHV-6 type B activity infection could associate with MS.3. The results from comparing MS with NNID patients and healthy controls indicated that HHV-6 type B primary infection could associate with MS.4. The results from comparing MS with NID patients and NNID patients indicated EBV primary infection could associate with MS.