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.

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Учредитель и издатель Федеральное государственное бюджетное образовательное учреждение высшего образования «Алтайский государственный медицинский университет» Министерства здравоохранения Российской Федерации (ФГБОУ ВО АГМУ Минздрава России) 656038, РФ, Алтайский край, Барнаул, проспект Ленина, 40 www.asmu.ru РЕДАКЦИЯ Главный редактор Салдан Игорь Петрович доктор медицинских наук, профессор Заместитель главного редактора Жариков Александр Юрьевич доктор биологических наук, доцент Редактор-организатор Киселев Валерий Иванович член-корреспондент РАН, доктор медицинских наук, профессор Выпускающий редактор Широкоступ Сергей Васильевич кандидат медицинских наук, доцент Научные редакторы Брюханов Валерий Михайлович доктор медицинских наук, профессор Колядо Владимир Борисович доктор медицинских наук, профессор Лукьяненко Наталья Валентиновна доктор медицинских наук, профессор Шойхет Яков Нахманович член-корреспондент РАН, доктор медицинских наук, профессор Редакционная коллегия Брико Николай Иванович академик РАН, доктор медицинских наук, профессор Воевода Михаил Иванович академик РАН, доктор медицинских наук, профессор Дыгай Александр Михайлович академик РАН, доктор медицинских наук, профессор Злобин Владимир Игоревич академик РАН, доктор медицинских наук, профессор Лобзин Юрий Владимирович академик РАН, доктор медицинских наук, профессор Мадонов Павел Геннадьевич доктор медицинских наук, профессор Онищенко Геннадий Григорьевич академик РАН, доктор медицинских наук, профессор Павлова Наталья Григорьевна доктор медицинских наук, профессор Полушин Юрий Сергеевич академик РАН, доктор медицинских наук, профессор Рахманин Юрий Анатольевич академик РАН, доктор медицинских наук, профессор Ответственный за перевод Широкова Валерия Олеговна БЮЛЛЕТЕНЬ МЕДИЦИНСКОЙ НАУКИ №3 (11) 2018 2 СОДЕРЖАНИЕ Науки о здоровье Влияние минеральной воды на течение экспериментальной гастропатии Онищенко Г.Г.

The Relapsing-Remitting Multiple Sclerosis (MS) patients research has revealed that the matrix metalloproteinase-2 level in cerebrospinal fluid which is higher then 30 ng/ml during the relapse and/or remission period increases repeated relapse risk during 2 years term by 2.8 times. The rapid MS progressing is associated with the high level of adhesion molecule (sPECAM) in cerebrospinal fluid.

According to the anamnesis data 38% of multiple sclerosis patient population had neuritis retrobulbaris as the first clinical symptom. The examination of visual evoked potentials detected that 88% of patients who had suffered from neuritis retrobulbaris earlier, and 19% of those, who had not, had changes revealing possible subclinical demyelinization of a visual nerve.

We evaluated the influence of hypoxic hypoxia on lactate, creatinine and urea concentrations in the amniotic fluid (AF) of rabbits on 27-28th day of pregnancy. Rabbits were randomly sudivided into two groups: experimental (n=9) and control (n=6). Rabbits of experimental groups were placed in a hypoxic chamber containing 10±2% oxygen and 90±2% nitrogen for 1 h and then were euthanized, AF was extracted from the amniotic sacs via disposable syringe. Acute hypoxic hypoxia had no effect on the AF volume, increased (1.4-fold) lactate, (1.3-fold) creatinine and (1.1-fold) urea concentrations in AF. In contrast to animals of the control group, lactate concentration in the groups with hypoxic hypoxia correlated with the creatinine (r=0.71, p<0.0001, n=35) and urea concentrations in the AF (r=0.81, p<0.0001, n=35). These results suggest that acute hypoxic hypoxia in late pregnancy causes changes in the biochemical composition of AF; these changes are characterized by high lactate concentrations, and the fetus and uterus can be the source of increased lactate level in AF.

In liquor 30 multiple sclerosis patients with remittent kind of clinical course the concentration of cell-cell adhesion molecules (sPECAM-1, sVCAM-1) and tumor necrosis factor (TNF) α, not interleukin-1β, was higher during the period of exacerbation compared to the period of remission. These changes are supposed to display the activity of pathogenesis important processes multiple sclerosis in cerebral tissue of multiple sclerosis patients.