Multilocus evaluation of genetic predictors of multiple sclerosis.

BACKGROUND: Genome-wide association studies identified numerous susceptibility loci for multiple sclerosis in populations of European ancestry, but the associations are not always reproducible in other populations due to admixture and different linkage disequilibrium patterns obscuring true association signals. OBJECTIVE: Our aim was to identify genetic predictors of multiple sclerosis in three ethnically homogenous populations from the Volga-Ural region of Russian Federation. METHODS: In the largest to date study of multiple sclerosis in Russian population, involving 2048 participants from the Republic of Bashkortostan, Russian Federation (641 patients with multiple sclerosis and 1407 unaffected individuals), we performed replication analysis of previously identified genome-wide signals for multiple sclerosis. Associations were tested using logistic regression analysis under additive genetic model adjusted for sex. Meta-analysis of the study results in three populations was performed under fixed effects and random effects models. RESULTS: We demonstrate the association with multiple sclerosis of the five variants (INAVA rs7522462, EOMES rs11129295, C6orf10 rs3129934, CD86 rs9282641, and GPR65 rs2119704). The strongest association (OR = 2.16, CI:1.85-2.74, P = 2.53x10-13) was detected for rs3129934 polymorphism in the major histocompatibility region. Multilocus analysis has revealed 322 and 27 allelic patterns associated with multiple sclerosis in women and men, respectively. In women, the highest risk of MS was conferred by C6orf10 rs3129934*T/T + STAT3 rs744166*T combination (OR = 11.87), in men - by C6orf10 rs3129934*T + EOMES rs11129295*C + RPS6KB1 rs180515*C combination (OR = 3.25). CONCLUSION: We confirm five associations with multiple sclerosis previously reported in genome-wide scans in Europeans in three ethnic groups from the Volga-Ural region of Russia.

Multilocus associations of inflammatory genes with the risk of type 1 diabetes.

BACKGROUND: Genome-wide association studies have captured a large proportion of genetic variation related to type 1 diabetes mellitus (T1D). However, most of these studies are performed in populations of European ancestry and therefore the disease risk estimations can be inaccurate when extrapolated to other world populations. METHODS: We conducted a case-control study in 1866 individuals from the three major populations of the Republic of Bashkortostan (Russians, Tatars, and Bashkirs) in Russian Federation, using single-locus and multilocus approach to identify genetic predictors of T1D. RESULTS: We found that LTA rs909253 and TNF rs1800629 polymorphisms were associated with T1D in the group of Tatars. Meta-analysis of the association study results in the three ethnic groups has confirmed the association between the T1D risk and LTA rs909253 genetic variant. LTA rs909253 and TNF rs1800629 loci were also featured in combinations most significantly associated with T1D. CONCLUSION: Our findings suggest that LTA rs909253 and TNF rs1800629 polymorphisms are associated with the risk of T1D both independently and in combination with polymorphic markers in other inflammatory genes, and the analysis of multi-allelic combinations provides valuable insight in the study of polygenic traits.

[The Role of Neurotrophins and Neurexins Genes in the Risk of Paranoid Schizophrenia in Russians and Tatars].

Schizophrenia affects about 1% of the population. Its etiology is not fully understood. Environmental conditions certainly contribute to the development of schizophrenia, but the determining factor is genetic predisposition: the coefficient of heritability of schizophrenia is about 80%, which is typical for the most highly heritable multifactorial diseases. Polymorphic loci of genes of enzymes and receptors involved in the processes of neuroprotection and neurotrophia play significant role in the development of this disease. In this paper we investigated 48 polymorphic variants of genes of the neurotrophins and neurexins family (BDNF, NTRK2, NTRK3, NGF, NXPH1, and NRXN1) in Russian and Tatar cases and in a control group living in the Republic of Bashkortostan. The results of this study confirm the important role of neurotrophin and neurexin genes in paranoid schizophrenia development.

Polymorphisms of inflammatory markers and risk of essential hypertension in Tatars from Russia.

Essential hypertension (EH) is a common disease with a clear genetic component. Inflammation and endothelial dysfunction play a prominent role in the development of persistent blood pressure elevation. The aim of the current study was to detect an association between EH and polymorphic markers in genes encoding for molecules involved in the control of intercellular interactions during the inflammation process. We analysed SNPs in SELE, SELP, SELL, ICAM1, VEGFA, IL1B, IL6, IL10 and IL12B genes in a group of 534 men of Tatar ethnicity (217 patients with EH and 317 controls). Using a Markov chain Monte-Carlo-based approach (APSampler), we found genotype and allelic combinations associated with EH. The most significant associations were observed for SELE rs2076059*C-SELP rs6131*A-VEGFA -2549*I-IL1B rs16944*C (p = 3.42 × 10(-5), FDR q = 0.035) and SELE rs2076059*C-SELP rs6131*A-IL12B rs3212227*C-IL1B rs16944*C (p = 323 × 10(-4), FDR q = 0.035).

[CYP2D6, CYP3A5, and CYP3A4 gene polymorphism in Russian, Tatar, and Bashkir populations].

The allele and genotype frequency distribution at polymorphic loci rs3892097 (184G>A) of CYP2D6 gene, rs776746 (6986A>G) of the CYP3A5 gene and rs2740574 (-392A>G) of the CYP3A4 gene in Russians, Tatars, and Bashkirs was examined. Samples were taken from residents of Bashkortostan Republic (1240 men and women aged from 20 to 109 years and consisted of 443 Russians, 517 Tatars, and 280 Bashkirs). Allele identification was conducted using PCR-RFLP or PCR with TaqMan probes. The "nonfunctional" allele rs3892097*A of the CYP2D6 gene was detected in populations of Russians, Tatars, and Bashkirs in 17.2, 9.5, and 7.1% cases, respectively. The rs776746*G allele of the CYP3A5 gene encoding the CYP3A5 isoenzyme with decreased activity was revealed with a frequency of 94.6% in populations of Russians, 94.3% in the Tatar population, and 91.5% in the Bashkir population. The share of the minor allele rs2740574*G of the CYP3A4 was 4.0% in populations of Russians, 0.5% in the Tatar population, and 0.9% in the Bashkir population. It has been previously shown that the rs3892097*A, rs776746*G, and rs2740574*G allele frequencies vary significantly in different world populations. Since allele variants of CYP2D6, CYP3A5, and CYP3A4 genes can play essential role in interindividual and in interethnic differences in the metabolism of many therapeutic agents, the obtained results could be used in the prognosis of pharmacotherapy efficacy in populations of Russians, Tatars, and Bashkirs.

[The association of risk of development of cardiomyopathies with polymorphic variants of genes of angiotensin converting enzyme, glutathione-S-transferase, interleukins 8 and 10].

The article presents the results of study of association of risk of development and clinical course of cardiomyopathies with polymorphic variants of genes ACE, GSTM1, IL8 and IL10. The purpose of research was to find out molecular genetic markers of risk of development and clinical course of various types of cardiomyopathies. The analysis used the DNA samples extracted from lymphocytes of peripheral venous blood of patients with cardiomyopathies (N = 89) and control group (N = 426). The standard analysis techniques of polymerase chain reaction and restriction fragment length polymorphism were applied to detect polymorphic loci of genes candidates. It is established that genotype of DD-polymorphic locus of I/DgeneACE is a marker of development of ischemic cardiomyopathy. The allele D is a marker of development of increased rate of manifestation of extra-systoles, growth of inter-ventricular septum and reduction of fraction of discharge in patients with cardiomyopathies.

[Age-dependent CYP1A2 gene polymorphism -163C>A in three ethnic groups of Bashkortostan Republic residents].

On a sample of 1240 persons from Bashkortostan, including Russian, Bashkirs and Tatars, the analysis of allele and genotype frequencies distribution of CYP1A2 gene polymorphism -163C>A was performed by PCR-RFLP in view of belonging to a particular age cohort. In Russian and Bashkirs ethnic groups we observed age-dependent decrease of CYP1A2*C allele and CYP1A2*CI*C genotype frequencies (in Russian statistically significant for allele and genotype, the Bashkirs--only for allele) and a statistically significant increase of CYP1A2*A allele and CYP1A2*A/*A genotype frequencies. The set reduction in the frequency of the wild allele CYP1A2*C and increasing the frequency of the mutant allele CYP1A2*A with age may be due to greater survival of persons who are carriers of that allelic variants of CYP1A2 gene, providing a more efficient metabolism of xenobiotics.

[Frequency of CHEK2 gene mutations in patients with breast cancer from the Republic of Bashkortostan].

Several studies have shown, that mutation in CHEK2 gene can increase the risk of different cancers, including breast cancer (BC). Clearly, that character of mutations distribution in the defined regions is depended on genetic structure of the population. We conducted the screening of mutations c.1100delC, c.444 + 1G>A, de15395, p.I157T andIp.R145Win CHEK2 gene in patients with breast cancer (n = 977) and in control group (n = 1069) originating from the Republic of Bashkortostan. The mutation de15395 in CHEK2 gene was detected with frequency of 1,23% (12/977)in woman with BC and 0.09% (1/1069) in controls (OR:13.28, CI 95%: 1.72-102.33, p = 0.003). Mutations c.1100delC and c.444 + 1G>A were found in BC patients and controls with frequencies of 0.4%, 0.4% (4/977) and 0.09% (1/1069), 0.2% (2/1069), respectively. The missense mutation p.I157T in CHEK2 was found as the most common variant in two studied cohorts (approximately 5%), but differences did not achieved statistical significance. We found the ethnic specificity in distribution of truncating mutations, which occurs mainly among the women of Slavic origin. All three mutations were identified in women of Russian and Ukrainian ethnic origin. Mutations c.1100delC and c.444 + 1G>A in CHEK2 gene were not detected in Bashkirs and Tatars, but CHEK2 de15395 mutation was observed in Tatars.

[Glutamate receptors genes polymorphism and the risk of paranoid schizophrenia in Russians and tatars from the Republic of Bashkortostan].

Schizophrenia is a severe mental disorder that affects about 1% of the world population, leading to disability and social exclusion. Glutamatergic neurotransmission is a violation of one of the main hypotheses put forward to explain the neurobiological mechanisms of schizophrenia. Post mortem studies have found changes in the degree of affinity glutamate receptors, their transcription, and altered expression of their subunits in the prefrontal cortex, hippocampus, and thalamus in patients with schizophrenia. As a result of genetic studies of gene family encoding ionotropic AMPA and kainate glutamate receptors in schizophrenia, ambiguous results were received. The association of polymorphic variants of genes GRIA2 and GRIK2 with paranoid schizophrenia and response to therapy with haloperidol in Russian and Tatar of the Republic of Bashkortostan was conducted in the present study. DNA samples of 257 patients with paranoid schizophrenia and of 349 healthy controls of Russian and Tatar ethnic group living in the Republic of Bashkortostan were involved into the present study. In the result of the present study: (1) high risk genetic markers of paranoid schizophrenia (PSZ) were obtained: in Russians-GR4IA2*CCC (OR = 9.60) and in Tatars-GRIK2*ATG (OR = 3.5), GRIK2*TGG (OR = 3.12) (2) The following low risk genetic markers of PSZ were revealed: in Tatars-GRIA2*T/T (rs43025506) of GRIA2 gene (OR = 0.34); in Russians.- GRIA2*CCT (OR = 0.481). (3) Genetic markers of low haloperido! treatment efficacy in respect of negative and positive symptoms GRIK2*T/T (rs2227281) of GRIK2 gene and GRAL42*C/C in Russians, GRIK2*A/A (rs995640) of GRIK2 gene in Tatars. (4) Genetic markers of low haloperidol treatment efficacy in respect of positive symptoms GRL42*C/C in Russians. The results of the present study support the hypothesis of the involvement of glutamate receptor genes in schizophrenia pathway. Considerable inter-ethnic'diversity of genetic risk factors for this disease was revealed.

[Polymorphism of DNA repair genes (XRCC1, XRCC3, XPC, XPD, XPA) in ethnic groups from Republic of Bashkortostan].

Genotype and allele-frequency distributions of the excision and homologous recombination of DNA repair genes XRCC1 (rs25487 and rs25489), XRCC3 (rs861539), XPC (rs2228001), XPD (rs13181), XPA (rs1800975) were examined in three ethnic groups from the Republic of Bashkortostan (Russia), Russians, Tatars, and Bashkirs. The data obtained were compared to those for other ethnic groups from Russia and worldwide. Statistically significant differences in the allele-frequency distribution of the XPA gene polymorphic locus rs1800975 (p = 0.03) between the samples of Russians and Tatars were demonstrated. Russians and Bashkirs differed in the allele-frequency distribution of the rs861539 polymorphic locus of the XRCC3 gene (p < < 0.0001), and Tatars and Bashkirs, at the rs861539 locus of the XRCC3 gene (p < 0.0001). In Russians and Tatars from the Republic of Bashkortostan, allele frequencies at the DNA repair gene polymorphic loci examined were consistent with those in the population of Northern and Western Europe, while polymorphic allele-frequency distributions in Bashkirs was similar to that observed in the ethnic group of Gujarati Indians.

[Association polymorphic variants of GRIN2B gene with paranoid schizophrenia and response to common neuroleptics in Russians and Tatars from Bashkortostan Republic].

An analysis of the association of paranoid schizophrenia seeking with polymorphic variants of GRIN2B gene was performed in order to identify genetic risk factors of disease development and genetic markers of the response to therapy by neuroleptics in Russian and Tatar patients from Bashkortostan Republic (BB). In the course of the analysis, we revealed the following: 1) genetic markers of increased risk of developing paranoid schizophrenia in various ethnic groups, including, in Tatars, the GRIN2B* T/*Tgenotype (p = 0.003; OR = 2.33) and GRIN2B*T allele (p = 0.001; OR = 2.36), rs1805247; in Russians, the GRIN2B*T/*T genotype (p = 0.038; OR = 2.12) and GRIN2B* T allele (p = 0.028; OR = 2.03), rs1805247, genotype GRIN2B*A/*A (p = 0.042; OR = 2.12), rs1805476; 2) genetic markers of the reduced risk of developing paranoid schizophrenia; 3) genetic markers of therapy response and the risk of side effects development during neuroleptics (haloperidol) treatment in Bashkortostan. The significant interethnic diversity of genetic factors related to the risk of this disease development was noted.

[Role of dopamine transporter gene (DAT1) polymorphisms in personality traits variation].

According to psychobiological model of personality proposed by Cloninger, personality traits characterizing enhanced tendency to novel stimuli, impulsivity and sociability are influenced by dopaminergic system functioning. The present study considered both the main effect of two polymorphic loci (VNTR and 2319G>A) in dopamine transporter gene (DAT1) and the role of distinct DAT1 gene haplotypes in personality traits variation in 592 healthy individuals belonging to different ethnicities (men and women). The results of the study revealed the involvement of VNTR and 2319G>A polymorphisms in Novelty Seeking variation and the main effect of 2319G>A polymorphism on Reward Dependence (TCI) observed in Russian females. Moreover, DAT1 gene haplotype effect on Novelty Seeking in Russian females and on Persistence (TCI) in Tatar females was demonstrated. Reported in the current study results pointed to the involvement of dopaminergic system (DAT1 gene in particular) in variation of personality traits characterizing the tendency to novel stimuli, purposefulness, and sociability specifically in women.

[Genetic epidemiological study of Bashkortostan Republic: the effect of genetic structure of population on the load of monogenic hereditary diseases].

Here we present the data obtained during medical genetic examination of the population of five districts of Bashkortostan Republic (Burzyanskii, Baimakskii, Abzelilovskii, Salavatskii, and Arkhangelskii) populated with 168050 persons including 135748 Bashkirs. The study involved all the population of the districts including each ethnic group and was conducted according to standard protocol developed in the Laboratory of Genetic Epidemiology, Medical Genetic Research Center, Russian Academy of Medical Sciences. Based on segregation analysis, the values of prevalence rates of the major types of Mendelian pathology (AD, AR, and X- linked diseases) was calculated in five regions of the Republic as well as for Bashkirs alone. Significant differences in the prevalence rates of AD and AR pathologies between individual districts, in particular upon division in rural and urban population, was observed. The prevalence rates comparison of monogenic hereditary pathology among Bashkirs compared to other previously examined populations have shown that the patterns of the hereditary disease load in the inspected districts of Bashkortostan were similar to that observed in the population of some districts in Udmurtia, Marii El and Chuvashiya. Russian European populations have shown significantly lower load of hereditary diseases. Correlation analysis of local inbreeding, endogamy and prevalence rates of AD and AR pathologies has shown that development of hereditary diseases load is significantly affected by gene drift.

[Marriage migration parameters in six rural districts of Bashkortostan Republic].

The marriage migration structure of the populations of six districts of Bashkortostan Republic has been studied. The rates of assortative marriages in Bashkirs, Tatars, and Russians are 1.02-2.71, 1.30-5.99, and 2.14-7.50, respectively; the endogamy indices are 0.58-0.97, 0.90, and 0.68, respectively. Malecot's isolation-by-distance parameters in Bashkirs, Tatars, and Russians, respectively, are the following: sigma is 6.7-83.0, 40.3-106.1, and 69.9; a is 0.00012-0.00074, 0.00170-0.0029, and 0.00096; and b is 0.0087-0.0467, 0.0038-0.0208, and 0.0129. Changes in these parameters with time have been traced.

[Spectrum and frequency of mutations in the connexin 32 gene (GJB1) in hereditary and sensory neuropathy type 1X patients from Bashkortostan].

Hereditary motor and sensory neuropathy type 1X (HMSN 1X) is the second most frequent form of demyelinating polyneuropathies and is caused by mutations in the gene for connexin 32 protein (Cx32, GJB1). The contribution of HMSN 1X to the structure of HMSN in the Republic of Bashkortostan was determined. The GJB1 mutations were detected in 18 out of 131 unrelated patients, which constituted 13.7%. The four missense mutations identified were represented by: Pro87Ala (c.259C>G) with the frequency of 10%; Arg22Gln (c.65G>A) (2.98%); Arg15Gln (c.44G>A); and Thr86Ile (c.257C

[Association of cytochrome P450 genes polymorphisms (CYP1A1 and CYP1A2) with the development of chronic obstructive pulmonary disease in Bashkortostan].

To assess the role that polymorphisms of cytochrome P450 genes play in genetic predisposition to chronic obstructive pulmonary disease (COPD), the allele and genotype distributions of CYPIA1 (2455 A/G, 3801T/C) and CYP1A2 (-2464T/delT, -163C/A) genes were studied in Tatar and Russian COPD patients and in cases of healthy individuals (Russian, Tatar and Bashkir), residents of Bashkortostan. It was shown that the CYP1A1 and CYP1A2 genes haplotypes frequency distribution patterns do not differed between Tatars and Russians ethnic groups (chi2 = 0.973, df = 3, p = 1.00 and chi2 = 1.546, df = 3, p = 0.92, respectively). Analysis of the the CYP1A1 and CYP1A2 genes haplotypes revealed statistically significant differences in the haplotypes frequency distributions between Bashkirs versus Russians and Tatars (chi2 = 12.328, df= 3,p = 0.008; chi2 = 9.218, df=3, p = 0.034, respectively for CYP1A1 gene and (chi2 = 18.779, df=3, p = 0.0001, chi = 14.326, df=3, p = 0.003, respectively for CYP1A2 gene). The (-2467)delT allele and CYP1A2*1D haplotype of CYPIA2 gene was associated with higher risk of COPD in Tatar ethnic group (OR = 1.83, 95% CI 1.24-2.71, chi2 = 9.48, p = 0.003 and chi2 = 9.733, p = 0.0027, Pcor = 0.008; OR = 3.908, 95% CI 1.56-10.19, respectively). On the other hand the CYP1A2*1A haplotype had protective effect (chi2 = 6.319, p = 0.0127, Pcor = 0.038; OR = 0.6012, 95% CI 0.402-0.898). But at the same time we did not find any differences in the genotypes and haplotypes frequency distributions of the CYP1A2 gene within the patients and healthy groups in Russian ethnic group. We also did not find any association of CYP1A1 gene with COPD in ethnic groups of Bashkortostan.

Association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension in Tatars from Russia.

Essential hypertension is a common disease with fatal clinical complications. Epidemiological and family studies have confirmed the role of genetic predisposition in its development. Hypertensive patients have been shown to have an altered profile of pro- and anti-inflammatory cytokines. The aim of our investigation was to reveal the association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension and its clinical complications in a Tatar ethnic group from Bashkortostan, Russia. The study involved 362 hypertensive patients and 244 healthy subjects from this Tatar ethnic group (Bashkortostan, Russia). DNA was isolated from whole venous blood using phenol-chloroform extraction by the standard method. IL6 -572 G/C, IL12B 1159 C/A, and IL10 -627 C/A genotypes were typed using polymerase chain reaction followed by restriction enzyme digestion. We found that the IL10 -627 *C/*C genotype was associated with decreased risk of hypertension (OR = 0.64, P = 0.035). IL6 genotypes and allele distribution did not differ significantly between subjects with and without hypertension, but the IL6 -572 *G/*G genotype frequency was found to be significantly higher among those patients who had stroke, compared with normotensive control subjects (P = 0.036). Carriers of the IL12B 1159 *A/*A genotype had a lower risk of stroke (OR = 0.38, P = 0.028). Our study has shown the association between IL10 -627 C/A polymorphism and essential hypertension in the Tatar ethnic group from Bashkortostan, Russia. The IL10 -627*C/*C genotype was found to be protective against hypertension. We also demonstrated that hypertensive patients with the IL12B *A/*A and IL6 *G/*G genotypes had increased risk of stroke. Our results suggest a role for cytokines in cardiovascular disease development in the Tatar ethnic group, but further investigation is needed.

[Analysis of the cytochrome P450 (CYP1A1) gene polymorphism in the ethnic groups of the Republic of Bashkortostan].

In three ethnic groups from the Republic of Bashkortostan, Russians (N = 451), Tatars (N= 333), and Bashkirs (N= 171), allele, genotype, and haplotype frequency distribution patterns of the CYP1A1 gene single nucleotide polymorphisms, A2455G and T33801C, were investigated. Substantial interethnic differences in the allele frequency distribution patterns of the CYPIA1 polymorphisms A2455G and T3801C (chi2 = 15.61, d.f. = 2, P = 0.0001; and chi2 = 22.10, d.f. = 2, P = 0.0001, respectively) were observed. Pairwise comparison showed that ethnic groups of Tatars and Russians were similar in the A2455G allele frequencies (chi2 = 1.10, d.f. = 1, P = 0.30). However, in case of the T3801C marker, statistically significant differences were revealed (chi2 = 4.56, d.f. = 1, P = 0.032). At the same time, Bashkir ethnic group was found to be statistically significantly different from Russians and Tatars in the CYP1A1 polymorphic allele frequency distribution patterns (chi2 = 15.74, d.f. = 2, P = 0.0001; and chi2 = 7.47, d.f. = 1, P = 0.024, for A2455G, and chi2 = 6.46, d.f. = 1, P = 0.011; and chi2 = 21.36, d.f. = 1, P = 0.0001, for T3801C). Analysis of the CYP1A1 haplotype diversity showed that in terms of the CYP1A1 haplotype frequency distribution patterns, Bashkir ethnic group was statistically significantly different from both Russians (chi2 = 30.07, d.f. = 3, P = 0.0001) and Tatars (chi2 = 11.28, d.f. = 3, P = 0.013). The differences observed were caused by the high frequency of haplotype CYP1A1*2B, which was represented by a combination of rare alleles of the CYP1A1 polymorphisms A2455G and T3801C in Bashkirs (5.81%). On the other hand, the ethnic groups of Russians and Tatars residing in the Republic of Bashkortostan were characterized by similar frequencies of the CYP1A1 haplotypes (chi2 = 6.322, d.f. = 3, P = 0.127). The data obtained could be used in further investigations of the genetic bases of ecology dependant diseases and in the risk groups in the Republic of Bashkortostan.

Variation of skeletal biomarkers of biological aging in a Chuvashian population: a longitudinal study.

Osseographic score (OSS) is a skeletal biomarker of biological aging, based on assessment of the hand's radiographic features. The aims of the present cross-sectional and follow-up study were: 1) to evaluate age-related changes of OSS in a large Chuvashian cohort, and 2) to evaluate sex differences in age-related changes of OSS. This study reports on intersexual differences in the pattern of skeletal aging. The most prominent difference was in the rate of skeletal change, measured as average OSS difference per year. However, no differences were found in the age at which the first skeletal change occurred. The mean values of OSS were higher in males than in females in decades 3-5 of life, but afterwards they reversed. In a follow-up study, we found that sex differences regarding the rate of OSS change began in the fifth decade, but became statistically significant only in the sixth and seventh decades. Thereafter, the rate of OSS change again became virtually equal between sexes.

[Genotypes of vitamin-D-binding protein (DBP) in patients with chronic obstructive pulmonary disease and healthy population of Republic Bashkortostan].

The distribution of alleles and genotypes of vitamin D-binding protein (DBP) gene has been studied in patients with Chronic Obstructive Pulmonary Disease (COPD, n = 298) and healthy individuals (n = 237) from two ethnic groups (Tatars and Russians) living in Republic Bashkortostan. Statistically significant differences in the distribution of DBP gene genotypes between Tatars and Russians (chi2 = 8.854, df = 5, P = 0.04) were revealed. The pattern of allele's distribution within DBP gene was similar in healthy control subjects of both ethnic groups, with gradient reduction in row GC*1S> GC*1F> GC*2. The most common genotypes were: GC*1F/1S in Tatars (36.79%) and GC*1S/2 in Russians (34.62%). It has been shown, that Tatars with genotype GC*1F/1S have a lower risk of COPD development: the frequency of GC*1F/1S genotype in COPD patients was significantly lower than in healthy individuals (19.85% versus 36.79%; chi2 = 7.622, P = 0.0067, Pcor = 0.0335; OR = 0.42 CI 95% 0.22-0.79). At the same time, COPD patients from the same group had higher frequency of GC* 1F/2 genotype than healthy individuals (19.08% versus 8.49%; chi2 = 4.52, P = 0.033, Pcor = 0.165; OR = 2.54 CI 95% 1.067-6.20). In Russian population the distribution of alleles and genotypes of DBP gene were similar in COPD patients and healthy individuals.