title: Association of SNPs of CD40 gene with multiple sclerosis in Russians.
abstract: Multiple sclerosis (MS) is a serious, incurable neurological disease. In 2009, the ANZgene studies detected the suggestive association of located upstream of CD40 gene in chromosome 20q13 (p = 1.3×10(-7)). Identification of the causal variant(s) in the CD40 locus leads to a better understanding of the mechanism underlying the development of autoimmune pathologies. We determined the genotypes of rs6074022, rs1883832, rs1535045, and rs11086996 in patients with MS (n = 1684) and in the control group (n = 879). Two SNPs were significantly associated with MS: rs6074022 (additive model C allele OR = 1.27, 95% CI = [1.12-1.45], p = 3×10(-4)) and rs1883832 (additive model T allele OR = 1.20, 95% CI = [1.05-1.38], p = 7×10(-3)). In the meta-analysis of our results and the results of four previous studies, we obtain the association p-value of 2.34×10(-12), which confirmed the association between MS and rs6074022 at a genome-wide significant level. Next, we demonstrated that the model including rs6074022 only sufficiently described the association. From our analysis, we can speculate that the association between rs1883832 and MS was induced by LD, whereas rs6074022 was a marker in stronger LD with the functional variant or was the functional variant itself. Our results indicated that the functional variants were located in the upstream region of the gene CD40 and were in higher LD with rs6074022 than LD with rs1883832.
authors.affiliation: Pharmacogenomics Group, Institute of Chemical Biology and Fundamental Medicine, Siberian Division, Russian Academy of Sciences, Novosibirsk, Russia. sokolovaea2608@gmail.ru
authors.forename: Ekaterina Alekseevna
authors.initials: EA
authors.lastname: Sokolova
authors.forename: Nadezhda Alekseevna
authors.initials: NA
authors.lastname: Malkova
authors.forename: Denis Sergeevich
authors.initials: DS
authors.lastname: Korobko
authors.forename: Aleksey Sergeevich
authors.initials: AS
authors.lastname: Rozhdestvenskii
authors.forename: Anastasia Vladimirovna
authors.initials: AV
authors.lastname: Kakulya
authors.forename: Elena Vladimirovna
authors.initials: EV
authors.lastname: Khanokh
authors.forename: Roman Andreevich
authors.initials: RA
authors.lastname: Delov
authors.forename: Fedor Alekseevich
authors.initials: FA
authors.lastname: Platonov
authors.forename: Tatyana Yegorovna
authors.initials: TY
authors.lastname: Popova
authors.forename: Elena Gennadievna
authors.initials: EG
authors.lastname: Aref' eva
authors.forename: Natalia Nikolaevna
authors.initials: NN
authors.lastname: Zagorskaya
authors.forename: Valentina Mikhailovna
authors.initials: VM
authors.lastname: Alifirova
authors.forename: Marina Andreevna
authors.initials: MA
authors.lastname: Titova
authors.forename: Inna Vadimovna
authors.initials: IV
authors.lastname: Smagina
authors.forename: Svetlana Alksandrovna
authors.initials: SA
authors.lastname: El' chaninova
authors.forename: Anna Valentinovna
authors.initials: AV
authors.lastname: Popovtseva
authors.forename: Valery Pavlovich
authors.initials: VP
authors.lastname: Puzyrev
authors.forename: Olga Georgievna
authors.initials: OG
authors.lastname: Kulakova
authors.forename: Ekaterina Yur'evna
authors.initials: EY
authors.lastname: Tsareva
authors.forename: Olga Olegovna
authors.initials: OO
authors.lastname: Favorova
authors.forename: Sergei Gennadievich
authors.initials: SG
authors.lastname: Shchur
authors.forename: Natalia Yurievna
authors.initials: NY
authors.lastname: Lashch
authors.forename: Natalia Fyodorovna
authors.initials: NF
authors.lastname: Popova
authors.forename: Ekaterina Valerievna
authors.initials: EV
authors.lastname: Popova
authors.forename: Evgenii Ivanovich
authors.initials: EI
authors.lastname: Gusev
authors.forename: Aleksey Nikolaevich
authors.initials: AN
authors.lastname: Boyko
authors.forename: Yurii Sergeevich
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Maxim Leonidovich
authors.initials: ML
authors.lastname: Filipenko
mesh_terms: D000328:Adult; D000483:Alleles; D019013:CD40 Antigens / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012426:Russia
chemical_list: D019013:CD40 Antigens