[The association of polymorphisms of the serotonin transporter gene SLC6A4 with depression]. / Svyaz' polimorfizmov gena serotoninovogo transportera SLC6A4 s depressiei.

OBJECTIVE: To study the relationship of polymorphic variants of the SLC6A4 gene with depression among people aged 25-44 years in Novosibirsk. MATERIAL AND METHODS: Under the WHO program «MONICA-psychosocial (MOPSY)¼, a random representative sample of people aged 25-44 years from the population of the Oktyabrsky district of Novosibirsk (men n=725, mean age 43.4±0.4 years, response - 71.3%, women n=710, mean age 44.8±0.4 years, response - 72%). Depression was assessed using the MONICA-MOPSY psychosocial questionnaire. Every fourth respondent was examined for polymorphic variants of 5HTTLPR-VNTR SNP rs25531 A>G of the SLC6A4 gene. The study was carried out within the framework of the budget topic Reg. No. 122031700094-5. RESULTS: The high level of depression among people aged 25-44 was 12.8% (for men 9.1%, for women - 15.92%); the average level of depression occurred in 24.5% of the population (among men in 21.24%, among women in 26.76%) (χ2=17.071, df=2, p<0.001). The most common genotype of the SLC6A4 gene, among people aged 25--4 years old in Novosibirsk, was SLA - 43.29%, LALA - 26.53% - in second place, SS - 17.87% - third, LALG - 6 genotypes were less represented genotypes. 74%, SLG - 4.18%, LGLG - 1.39%. Carrying the SLA genotype (53.3% and 63.6%) increased the chance of developing both the average level of depression by 2.359 (95% CI 1.278-4.355) times, and depression in general by 1.933 (95% CI 1.142-3.271) times, compared with persons carrying the LALA genotype (32.0% and 46.9%), (χ2=7.674, df=1, p<0.01 and χ2=6.095, df=1, p<0.05). Persons carrying the LALG genotype (54.5%) also had a higher chance of developing a mean level of depression RR=2.929 (95% CI 1.039-8.261), compared with carriers of the LALA genotype (32.0%) (χ2=4.326, df =1, p<0.05) (p<0.05). CONCLUSION: Associative links between polymorphic variants of the SLC6A4 gene and depression have been established.

Haplotype analysis of the HFE gene among populations of Northern Eurasia, in patients with metabolic disorders or stomach cancer, and in long-lived people.

BACKGROUND: Previously, it was shown that the HFE gene (associated with human hereditary hemochromatosis) has several haplotypes of intronic polymorphisms. Some haplotype frequencies are race specific and hence can be used in phylogenetic analysis. We assumed that analysis of Caucasoid patients-living now in Western Siberia and having diseases associated with dietary habits and metabolic rate-will allow us to understand the processes of possible selection during settling of the northern part of Asia. RESULTS: Haplotype analysis of Northern Eurasian native and recently settled ethnic groups was performed on polymorphisms rs1799945, rs1800730, rs1800562, rs2071303, rs1800708, rs1572982, rs2794719, rs807209, and rs2032451 of this gene. The CCA haplotype of the rs2071303, rs1800708, and rs1572982 was found to be associated with HLA-A2 (39 %) in Asian populations. Haplotype analysis for the rs1799945, rs1800730, rs1800562, rs2071303, rs1800708, and rs1572982 was performed on Russian patients with some metabolic disorders or stomach cancer and among long-lived people. Decreased frequencies of the TTA haplotype (T in rs2071303, T in rs1800708, and A in rs1572982) were observed in the groups of patients with diseases associated with overweight (fatty liver disease, type 2 diabetes mellitus, or metabolic syndrome + arterial hypertension) as compared with the control sample. We detected significant differences in this haplotype's frequency between the patients with type 2 diabetes mellitus and Russian adolescents, elderly citizens, and long-lived people (χ(2) P value = 0.003, 0.010, and 0.015, respectively). CONCLUSIONS: No significant differences in frequencies of the alleles with mutations in coding regions of the HFE gene (C282Y, H63D, and S65C) were detected between the analyzed patients (with stomach cancer, metabolic syndrome, fatty liver disease, or type 2 diabetes mellitus) and the control Caucasoid sample. Monophyletic origin of H63D (rs1799945) was confirmed in Caucasoids and Northern Asians. The reasons for a sharp increase in the frequency of CCA haplotype of HFE in the Asian race remain unclear.

[The Dynamics of the Composition of mtDNA Haplotypes of the Ancient Population of the Altai Mountains from the Early Bronze Age (3rd Millennium BC) to the Iron Age (2nd-1st Centuries BC)].

The mtDNA polymorphism in representatives of various archaeological cultures of the Developed Bronze Age, Early Scythian, and Hunnish-Sarmatian periods was analyzed (N = 34). It detected the dominance of Western-Eurasian haplotypes (70.6%) in mtDNA samples from the representatives of the ancient population of the Early Bronze Age--Iron Age on the territory of Altai Mountains. Since the 8th to the 7th centuries BC, a sharp increase was revealed in the Eastern-Eurasian haplogroups A, D, C, andZ (43.75%) as compared to previous cultures (16.7%). The presence of haplotype 223-242-290-319 of haplogroup A8 in Dolgans, Itelmens, Evens, Koryaks, and Yakuts indicates the possible long-term presence of its carriers in areas inhabited by these populations. The prevalence of Western-Eurasian haplotypes is observed not only in the Altai Mountains but also in Central Asia (Kazakhstan) and the South of the Krasnoyarsk Krai. All of the three studied samples from the Western-Eurasian haplogroups were revealed to contain U, H, T, and HV. The ubiquitous presence of haplotypes of haplogroup H and some haplogroups of cluster U (U5al, U4, U2e, and K) in the vast territory from the Yenisei River basin to the Atlantic Ocean may indicate the direction of human settlement, which most likely occurred in the Paleolithic Period from Central Asia.

[Gene Polymorphism of the c-fms, ITGB3,CCR2, and DBH genes in the populations of old believers of the Tyumen oblast and Russian residents of Novosibirsk].

Old Believers of the Tyumen oblast have been studied compared with a control sample of Russian residents of the city of Novosibirsk. The former are a unique subpopulation, which has been relatively isolated from the rest of Russians in central and northern regions of Russia due to religious reasons since the middle of the 17th century. Polymorphisms in the genes for glycoprotein ITGB3, dopamine-ß-hydroxylase (DBH), and chemokine receptor CCR2 and two mutations in the c-fms gene have been analyzed. The populations are only similar in the c-fms indel. The frequencies of the rare alleles of CCR2, ITGB3, and 3'UTR of c-fms in the Old Believers are lower than in the sample of Novosibirsk Russians, and the rare allele of DBH is more frequent. A significant negative correlation is observed between DBH and CCR2 (r =-0.88; df = 4; P < 0.023). Apparently, these differences are related to the long-term isolation of Old Believers. This assumption is consistent with the fact that the levels of heterozygosity for most loci in Old Believers are lower than in Novosibirsk Russians.

[Polymorphism of mitochondrial DNA in old believers from Siberia].

The polymorphism of mtDNA was examined in populations of Old Believers (n = 104) and Russians from Novosibirsk oblast (n = 270). Most of the haplogroups identified belonged to West Eurasian lineages. The frequencies of these haplogroups constituted 96.6% in Russians from Novosibirsk and 93.2% in Old Believers from Tyumen oblast. The populations examined were characterized by a high mtDNA diversity level (h = 0.98) compared to other population samples of Russians from Russia. Among the West Eurasian haplogroups, the most common (a frequency of more than 10%) were haplogroups H, U, J, and T, the proportion of which constituted 77.9% in Old Believers and 83.1% in Russians from Novosibirsk. The Mongoloid admixture in Russians (3.3%) and Old Believers (6.7%) was represented by haplogroups A, D, Z, and C, D, M*, respectively. Statistically significant differences (P < 0.05) were revealed between the Old Believers examined and Bosnians, Czechs, Slovenes, and Russians from the cities of Nizhny Novgorod and Tula. The data obtained confirm the earlier hypothesized influence of the Finno-Ugric component on the East Slavic populations.

[Haplotype diversity in mtDNA and Y-chromosome in populations of Altai-Sayan region].

Polymorphism of mtDNA was examined in five ethnic populations that belong to the Turkic language group and inhabit the territory of the Altai-Sayan upland (N = 1007). Most of the haplogroups identified in the examined populations belonged to East Eurasian lineages. In all five populations, only three haplogroups, C, D, and F, were prevailing. The frequencies of the other six haplogroups (A, B, G, M, Y, and Z) varied in the range from 1.1 to 6.5%. Among West Eurasian haplogrous, the most common were haplogroups H, J, T, and U. An analysis of Y-chromosome haplogroups in 407 individuals showed that only two haplogroups, N* and R1a1, were present in all five populations examined. Moreover, in different ethnic groups, the highest frequencies were observed for C-M130, N-P43, and N-Tat haplogroups. The differences in the distribution patterns of ancient West Eurasian and East Eurasian haplotypes from Gorny Altai in the present-day populations from the northern part of Eurasia revealed can be explained in terms of the multistage expansion of humans across these territories. The ubiquity of haplotypes from haplogroup H and cluster U across the wide territory from the Yenisei River basin to the Atlantic Ocean can indicate directional human expansion, which most likely occurred out of Central Asia as early as in the Paleolithic era, and took place in several waves with the glacier retreat.

[Mitochondrial DNA polymorphism in populations of aboriginal residents of the Far East].

An analysis of mtDNA polymorphism in eight populations of aboriginal residents (N = 519) of the Far East has been performed. The majority of haplogroups revealed in the examined groups were of East Eurasian origin. Haplogroup D was revealed in seven populations and its frequency varied from 2.8% in Koryaks to 28.3 and 28.9% in Nanaians and Evenks, respectively. Chukchi and Koryak populations, which belong to the same language family, exhibited haplogroup G, which has the same motive and indicates the genetic kinship of both populations. The presence of East Eurasian haplogroups A and D with a strong predominance of haplogroup A in Chukchi indicates the closer relationship of this population both with Asian and Canadian Eskimos and northern Atapasks on the other side of Bering Strait. The high level of genetic variability was revealed in populations belonging to the Tungus-Manjur group. The high frequency of east Eurasian haplogroups in Nanaians could result from close historical associations with Siberian Evenks.

[HFE gene polymorphism in the population of Northern Asia].

Human HFE gene haplotype analysis with reference to IVS2(+4)t/c, IVS4(-44)t/c, IVS5(-47)a/g polymorphic sites was performed in different North Asian ethnic groups. Of the eight possible intronic haplotypes, TTG, TTA, CTA and CCA were identified. High frequency of the CCA haplotype appears to be a characteristic feature of all Asian native populations. Potential functional importance of IVS4(-44)t/c polymorphism is demonstrated. Patients presenting with iron overload syndrome are shown to have low frequency of IVS4(-44)c.

Determination of HBsAg subtypes in Western Siberian part of Russia.

A set of monoclonal antibodies with specificity for hepatitis B surface antigen (HBsAg) was used for subtyping this antigen in sera from indigenous natives, blood donors, and drug users in Western Siberia with a modified commercial enzyme immunoassay kit for HBsAg detection. Three subtypes of HBsAg in a ratio of 36 (78%) ayw2:8 ayw3varB (18%):2 (4%) adw2 were found in 46 (100%) HBsAg-positive sera of different aboriginal populations of Western Siberia: the Tundra Nenets, Northern Khanty, Southern Altaians, and Kazakhs. Four subtypes of HBsAg in a ratio of 81 (57%) ayw2:58 (15 ayw3varA and 43 ayw3varB; 44%):2 (1%) adw2 were detected in 141 (100%) samples of blood donors from ten cities of Western Siberia. Three subtypes of HBsAg in a ratio of 34 ayw3:(both variants, 33 ayw3varA and 1 ayw3varB; 97.1%):1 (2.9%) ayw2 were found in blood of 35 injection drug users in Novosibirsk.