Variants of Interleukin-7/Interleukin-7 Receptor Alpha are Associated with Both Neuromyelitis Optica and Multiple Sclerosis Among Chinese Han Population in Southeastern China

Background： Neuromyelitis optica （NMO） and multiple sclerosis （MS） are autoimmune demyelinating diseases of the central nerve system, lnterleukin-7 （IL-7） and interleukin-7 receptor alpha （IL-7Rα） were proved to be important in the pathogenesis of both diseases because of the roles they played in the differentiations of autoimmune lymphocytes. The variants of both genes had been identified to be associated with MS susceptibility in Caucasian, Japanese and Korean populations. However, the association of these variants with NMO and MS has not been well studied in Chinese Southeastern Han population. Here, we aimed to evaluate the association of six IL-7 variants （rsl520333, rs1545298, rs4739140, rs6993386, rs7816065, and rs2887502） and one variant of IL-7RA （rs6897932） with NMO and MS among Chinese Han population in southeastern China. Methods： Matrix-assisted laser desorption/ionization time of flight mass spectrometry （MassARRAY system） and Sanger sequencing were used to determine the variants of IL-7 and IL-7RA in 167 NMO patients, 159 MS patients and 479 healthy controls among Chinese Han population in southeastern China. Samples were excluded if the genotyping success rate 〈90%. Results： Statistical differences were observed in the genotypes of IL-7 rs1520333 in MS patients and IL-7RA rs6897932 in NMO patients, compared with healthy controls （P = 0.035 and 0.034, respectively）. There was a statistically significant difference in the genotypes of IL-7 rs2887502 between MS and NMO patients （P = 0.014）. And there were statistically significant differences in the rs6897932 genotypes （P = 0.004） and alleles （P = 0.042） between NMO-IgG positive patients and healthy controls. Conclusions： The study suggested that among Chinese Hart population in southeastern China, the variant of IL-7RA （rs6897932） was associated with NMO especially NMO-IgG positive patients while the variant of IL-7 （rs1520333） with MS patients. And the genotypic differences of IL-7 rs2887502 between MS and NMO indicated the different genetic backgrounds of these two diseases.

No association between identified multiple sclerosis non-MHC risk loci and neuromyelitis optica

Neuromyelitis optica（NMO） and multiple sclerosis（ M S） a r e b o t h a u t o i m m u n e i n f l a m m a t o r y a n d demyelinating disorders of the central nervous system. Recently, more than 50 MS-susceptibility single-nucleotide polymorphisms（SNPs） have been detected outside the major histocompatibility complex（MHC） region. In this study, we aimed to evaluate the association of these identified non-MHC MS risk loci with Chinese patients with NMO. Thirtyfive non-MHC SNPs were selected and genotyped by matrix-assisted laser desorption/ionization timeof-fl ight mass spectrometry（MALDI-TOF MS） in 110 NMO patients and 332 controls from southeastern China. Among the 35 SNPs, only one, rs1800693 in the TNFRSF1 A locus, was nominally associated with NMO（P = 0.045, OR = 1.550, 95% CI = 1.007 – 2.384）. However, none of the 35 SNPs was associated with NMO after Bonferroni correction. Our results showed no association between these identified non-MHC MS risk loci and NMO, suggesting there are genetic differences in the etiology of NMO and MS.

Variants in the promoter region of CYP7A1 are associated with neuromyelitis optica but not with multiple sclerosis in the Han Chinese population

Multiple sclerosis（MS）and neuromyelitis optica（NMO）are common autoimmune demyelinating disorders of the central nervous system.The exact etiology of each remains unclear.CYP7A1was reported to be associated with NMO in Korean patients,but this is yet to be confirmed in other populations.In this study,we used Sanger sequencing to detect SNPs in the promoter region of CYP7A1 in a population consisting of unrelated patients and controls from the Han Chinese population（129 MS;89 NMO;325 controls）.Two known SNPs,204A〉C（rs3808607）and 469T〉C（rs3824260）,and a novel SNP（208G〉C）were identified in the 5＇-UTR of CYP7A1.The 204A〉C was in complete linkage with 469T〉C and both were associated with NMO but not with MS.Results suggest that the CYP7A1 allele was associated with NMO.NMO and MS have different genetic risk factors.This further supports the emerging evidence that MS and NMO are distinct disorders.

Variants of Interferon Regulatory Factor 5 are Associated with Neither Neuromyelitis Optica Nor Multiple Sclerosis in the Southeastern Han Chinese Population

Background： Neuromyelitis optica （NMO） and multiple sclerosis （MS） are demyelinating disorders of the central nervous system. Interferon regulatory factor 5 （IRF5） is a common susceptibility gene to different autoimmune disorders. However, the association of IRF5 variants with NMO and MS patients has not been well studied. Therefore, we aimed to evaluate whether IRF5 variants were associated with NMO and MS in the Southeastenl Han Chinese population. Methods： Four single nucleotide polymorphisnls （SNPs） were selected and genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry in 111 NMO patients, 145 MS patients and 300 controls from Southeastern China. Results： None of these 4 SNPs was associated with NMO or MS patients. Conclusions： Our preliminary study indicates that genetic variants in IRI~ may affect neither NMO nor MS in the Southeastern Han Chinese population. Further studies with a large sample size and diverse ancestry populations are needed to clarify this isstie.