+<Emphasis Type="Italic">276G</Emphasis>><Emphasis Type="Italic">T</Emphasis> single nucleotide polymorphism in the adiponectine (<Emphasis Type="Italic">APM1</Emphasis>) gene in donors from the Kharkiv population

+276G > T polymorphism in the adiponectine gene (APM1) was studied in 103 samples obtained from donors in the Kharkiv population (men/women: 64/38; 70 Ukrainian, 33 Russian). The T- and G-allele frequencies did not significantly differ between either men and women or between Russians and Ukrainians and comprised p _T = 0.55 and p _G = 0.45 in the general group. The genotype distribution deviated from the Hardy-Weinberg equilibrium: the heterozygote frequency was 1.55 times higher compared to the selectively neutral value, while the TT- and GG-homozygote frequencies were 0.55 and 0.33 of the equilibrium value, respectively.     

Q192R polymorphism of <Emphasis Type="Italic">PON-1</Emphasis> gene in type 2 diabetes patients

The Q192R polymorphism of PON-1 gene was genotyped in 96 individuals with diabetes mellitus type 2 (T2DM) and 123 nondiabetic control individuals from Kharkiv. Allele frequencies do not differ significantly between T2DM (p _Q = 0.65 and p _R = 0.35) and healthy individuals (p _Q = 0.70 and p _R = 0.30). Genotype distribution for healthy people complies with the Hardy-Weinberg equilibrium, and the T2DM patients have excess of both homozygotes and deficiency of heterozygotes. The risk of T2DM for QQ homozygotes is 1.47 times higher and for QR heterozygote is twice lower than the population average (2%). The RR homozygote individuals have statistically insignificant, 1.86 times, increase in T2DM risk.     

Polymorphism of Alcohol Dehydrogenase Gene <Emphasis Type="Italic">ADH1B</Emphasis> in Eastern Slavic and Iranian-Speaking Populations

Frequencies of alleles and genotypes for alcohol dehydrogenase gene ADH1B (arg47his polymorphism), associated with alcohol tolerance/sensitivity, were determined. It was demonstrated that the frequency of allele ADH1B*47his, corresponding to atypical alcohol dehydrogenase variant in Russians, Ukrainians, Iranians, and mountain-dwellers of the Pamirs constituted 3, 7, 24, and 22%, respectively. The frequencies established were consistent with the allele frequency distribution pattern among the populations of Eurasia. Russians and Ukrainians were indistinguishable from other European populations relative to the frequency of allele ADH1B*47his, and consequently, relative to specific features of ethanol metabolic pathways. The data obtained provide refinement of the geographic pattern of ADH1B*47his frequency distribution in Eurasia.     

Single nucleotide polymorphism of +276 g > t adiponectin (APM1) gene in donors of Kharkiv population

Polymorphism of adiponectine (APM1) gene in +276G > T position was studied. For this research we used blood samples of 103 donors (men/women: 65/38; 70 Ukrainian, 33 Russian) - habitants of Kharkiv. Frequencies of T and G alleles were pT = 0.55 and pG = 0.45 in a general group. They did not meaningfully differentiate either for men and women or for Russians and Ukrainians. Distribution of genotypes did not correspond to Hardy-Weinberg equilibrium: share of heterozygotes was 1.55 times higher than selectively-neutral value, share of TT homozygote is 0.55, and GG homozygote is 0.33 of equilibrium value.     

Approximation of the Basic Reproduction Number <Emphasis Type="Italic">R</Emphasis><Subscript>0</Subscript> for Vector-Borne Diseases with a Periodic Vector Population

The main purpose of this paper is to give an approximate formula involving two terms for the basic reproduction number R ₀ of a vector-borne disease when the vector population has small seasonal fluctuations of the form p(t) = p ₀ (1+ε cos (ωt − φ)) with ε ≪ 1. The first term is similar to the case of a constant vector population p but with p replaced by the average vector population p ₀. The maximum correction due to the second term is (ε²/8)% and always tends to decrease R ₀. The basic reproduction number R ₀ is defined through the spectral radius of a linear integral operator. Four numerical methods for the computation of R ₀ are compared using as example a model for the 2005/2006 chikungunya epidemic in La Réunion. The approximate formula and the numerical methods can be used for many other epidemic models with seasonality. MSC 92D30 ⋅ 45C05 ⋅ 47A55     

Glutathione peroxidase 1 (<Emphasis Type="Italic">GPX1</Emphasis>) single nucleotide polymorphism Pro198→Leu: Association with life span and coronary artery disease

In this study, we genotyped polymorphism in GPX1 Pro198→Leu (C→T) rs 1050450 in four groups, i.e., patients with coronary artery disease, people who lived a long time (over 90 years), people who died early (before 55 years) from cardiovascular disease, and the Russian population as a control group. We have found a significant higher T-allele frequency in men with coronary artery disease, i.e., 34.84% (χ² = 5.228, p = 0.022; OR =1.46), and in men who died early from cardiovascular diseases, 38.16% (χ² = 6.461, p = 0.011; OR = 1.69) compared to men in the control group, 26.8%. Moreover, a significantly higher genotype TT frequency has been shown in patients with coronary artery disease and myocardial infarction before age 50, which is 19.44% compared to the control group, which was 7.28% (χ² = 9.55, p = 0.002). The TT frequency in individuals who lived a long time (4.39%) was the lowest and differed significantly from the group with coronary artery disease, which was 12.79% (χ² = 8.07, p = 0.0045), and from the subgroup with coronary artery disease with myocardial infarction before age 50, which was 19.44% (χ² = 14.49, p = 0.0001). Thus, our results indicate that the TT allele (Leu) of GPX1 Pro198→Leu (C > T) polymorphism is unfavorable for successful aging; it leads to predisposition to coronary artery disease, early myocardial infarction (before age 50), and early death (before age 55).     

Effect of point substitutions in the <Emphasis Type="Italic">MnSOD,GPX1</Emphasis>, and <Emphasis Type="Italic">GSTP1</Emphasis> genes on the risk of familial and sporadic breast cancers in residents of Altai Krai

The frequencies of the polymorphic gene variants MnSOD Ala₉Val, GPX1 Pro₁₉₈Leu, and GSTP1 Ile₁₀₅Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T (rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58−0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05−2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.     

β3 Adrenergic Receptor Polymorphism and Obesity‐Related Phenotypes in Hypertensive Patients

Objectives: Obesity is a complex trait that is affected by both environmental and genetic risk factors. The β₃ adrenergic receptor (ADRB3) is expressed in adipose tissue and plays a role in energy metabolism. A missense mutation on codon 64 of this gene (W64R) is associated with receptor malfunction. Previous studies examining the relation between this polymorphism and obesity produced inconsistent findings. The current study assessed the association between the W64R genotype and obesity‐related phenotypes, including body weight, BMI, and serum triglycerides, cholesterol, and glucose. Research Methods and Procedures: We determined the ADRB3 W64R genotypes and fasting serum lipid and glucose concentrations for 695 hypertensive adults (336 men, 359 women) from a rural county in Anhui Province, China. Multivariate linear regression models were fit to detect associations between the genetic polymorphism and obesity‐related phenotypes. Results: The ADRB3 W64R polymorphism was significantly associated with body weight and BMI in men but not in women. After controlling for potential confounding variables, men who were homozygous for the R64 allele were 11.8 kg heavier (p < 0.001) and had a BMI that was 3.7 kg/m² greater (p = 0.001) than men who were homozygous for the W64 allele. Serum concentrations of lipids and glucose were found not associated with the genetic polymorphism. Discussion: The ADRB3 R64 allele was associated with increased body weight and BMI in men but not in women. The genetic association was not modified by triglyceride, cholesterol, blood glucose, or blood pressure levels of the subjects.     

Distribution of the HIV-1 Resistance-Conferring Alleles (CCR5delta32, CCR2-64I, and SDF1-3′A) in Russian, Ukrainian, and Belarusian Populations

The frequencies of three alleles, CCR5delta32, CCR2-64I, and SDF1-3A, known to decrease the risk of AIDS onset and the rate of the disease progression in HIV-infected individuals were determined in three native population samples from Russia, Ukraine, and Belarus. The frequencies of the alleles were 0.15, 0.12, 0.21; 0.12, 0.07, 0.20; and 0.12, 0.08, 0.26 for Russians, Ukrainians, and Belarussians, respectively. The proportion of the individuals without any of three protective alleles among Russians, Ukrainians, and Belarussians constituted 49, 65, and 61%, respectively. The genotype frequencies for the three loci studied were in Hardy–Weinberg equilibrium. Based on the three-locus genotype frequencies, the relative hazards of AIDS onset in HIV-infected individuals in each population were calculated as ranging from 0.79 to 0.88. In the samples of Eastern Slavs analyzed the estimated frequencies of the AIDS-protective alleles tested, as well as the frequencies of the corresponding genotypes and the relative hazards of AIDS onset were within the range of these parameters for the other European populations. The data on the allele frequencies and the relative hazard values in Russians, Ukrainians, and Belarussians can be used as the predictors of AIDS onset and progression rate in HIV-1-infected individuals from the populations studied.     

Analysis of the DRD4 Gene Polymorphism in Populations of Russia and Neighboring Countries

Allele and genotype frequencies of the VNTR polymorphism in the third exon of humanDRD4 gene were determined in 544 individuals living in Russia (Russians, Bashkirs, Tatars, and Mordovians) and in the neighboring countries (Kazakhs and Ukrainians). The data obtained were compared with the allele frequency distribution patterns reported for the populations of Eurasia. Similarly to other Eurasian populations, in our population samples R4 allele was prevalent (64 to 87%). The frequency of this allele in the populations of Western Europe constitute 61 to 71%, while in the populations of Asia it varies from 74 to 96%. In this respect, the populations studied occupied the intermediate position. In the samples examined the R7 allele frequency decreased from 7% in Ukrainians to 1% in Bashkirs, while in Kazakhs and Mordovians the allele was absent. This finding was consistent with theR7 allele distribution pattern in the populations of Eurasia, characterized by higher frequency in the West and lower frequency or absence of the allele in the East. In the group of 22 Eurasian populations, the R7 allele frequency negatively correlated with the frequency of the R4 allele (r = -0.86 at P < 0.001). Unlike the R4 and R7 alleles, the frequency of which changed in the eastward direction, the R2 allele frequency distribution displayed slightly expressed latitudinal increase southwards. The DRD4 genotype distribution deviated from the equilibrium in most of the samples examined. In some samples, statistically significant increase of the R2/R2homozygotes frequency was demonstrated. One of the possible explanations of this phenomenon is assortative mating with respect to phenotypic (behavioral) allele manifestation. The data obtained can serve as the basis for the investigation of the possible role of the DRD4 alleles as the risk factors for the development of alcoholism and other types of addictions.     

<Emphasis Type="Italic">M31R</Emphasis> and <Emphasis Type="Italic">R335C</Emphasis> polymorphic variants of the <Emphasis Type="Italic">IL8RA</Emphasis> gene in Russian and Buryat patients with atopic bronchial asthma

To test the M31R and R335C polymorphisms of the Il8RA gene for association with atopic bronchial asthma (BA), the allele and genotype frequency distributions of the polymorphisms were studied in Russian patients from Moscow and Buryat patients from Ulan-Ude. The study involved two Russian groups, one including 291 DNA samples of patients with atopic BA, and the other, 266 DNA samples of healthy people. The two Buryat groups included 124 and 152 DNA samples from patients with atopic BA and healthy people, respectively. The M31R polymorphism proved to be associated with atopic BA in Russians. Allele Arg and genotype Met/Arg suggested a higher risk of BA (OR = 4.45, P = 0.003 and OR = 4.58, P = 0.003, respectively), while allele Met and genotype Met/Met were associated with a lower risk (OR = 0.22, P = 0.003 and OR = 0.22, P = 0.003, respectively). The R335C polymorphism was not associated with atopic BA in Russians and was in Buryats. Allele Arg and homozygous genotype Arg/Arg suggested a higher risk of the disease (OR = 3.06, P = 0.030 and OR = 3.20, P = 0.027, respectively), while allele Cys and genotype Arg/Cys suggested a lower risk (OR = 0.33, P = 0.030 and OR = 0.31, P = 0.027, respectively). The results support the role of the IL8RA gene in atopic BA.     

Polymorphism of pigmentation genes (<Emphasis Type="Italic">OCA2</Emphasis> and <Emphasis Type="Italic">ASIP</Emphasis>) in some populations of Russia

In Russian populations, polymorphism of two pigmentation system genes, OCA2 (loci 305, 355, and 419, tested in Russians, Buryats, Chukchi, Koryaks, and Evens) and ASIP (locus 8818, tested in Russians and Buryats) was examined. Pairwise comparisons of the F _ST distances between the populations showed that only the populations from Northeast Asia (Chukchi, Koryaks, and Evens) were statistically significantly different from all other populations, at least relative to one of the OCA2 locus. In Russians from Pskov oblast and Novgorod oblast, increased frequency (up to 6%) of the OCA2 allele 419A was revealed. In earlier studies, as association of this allele with green eye color was demonstrated. The data obtained in terms of their application for ethnic population genetics.     

Sex-specific effects of <Emphasis Type="Italic">ACE</Emphasis> I/D and <Emphasis Type="Italic">AGT</Emphasis>-M235T on pulse pressure: the HyperGEN Study

Evidence shows that an elevated pulse pressure (PP) may lead to an increased risk of cardiovascular morbidity and mortality. There is also evidence that PP is a sexually dimorphic trait, and that genetic factors influence inter-individual variation in PP. The aim of this project was to assess the genotype-by-sex interaction on PP in a sample of mostly hypertensive African American and White participants using candidate genes involved in the renin–angiotensin–aldosterone system. Subjects were participants in the HyperGEN Study, including men (43%) and women (57%) over the age of 55 years (mean age = 65). Candidate gene polymorphisms used were ACE insertion/deletion (1,789 subjects genotyped) and AGT-M235T (1,800 subjects genotyped). We employed linear regression methods to assess the genotype-by-sex interaction. For ACE, genotype-by-sex interaction on PP was detected (P = 0.04): the “D/D” genotype predicted a 2.2 mmHg higher pulse pressure among women, but a 1.2 mmHg lower PP among men, compared to those with an “I” allele, after adjusting for age, weight, height, ethnicity, and antihypertension medication use. A similar interaction was found for systolic blood pressure. The genotype-by-sex interaction was consistent across ethnicity. The interaction was evident among those on antihypertensive medications (P = 0.05), but not among those not taking such medications (P = 0.55). In our analysis of AGT, no evidence of a genotype-by-sex interaction affecting PP, SBP, or DBP was detected. This evidence for a genotype-by-sex interaction helps our understanding of the complex genetic underpinnings of blood pressure phenotypes.     

The APOA4 Thr347→Ser347 Polymorphism Is Not a Major Risk Factor of Obesity

Objective: The goal of this study was to assess the association between the APOA4 Thr₃₄₇→Ser₃₄₇ polymorphism and BMI and obesity. Research Methods and Procedures: Men and women (n = 3320), randomly recruited in three independent population surveys from the north, east, and south of France, were genotyped for the APOA4 Thr₃₄₇→Ser₃₄₇ polymorphism. Results: There were 1327 overweight (825 men, 502 women) and 611 obese (313 men, 298 women) subjects. The prevalences of subjects carrying at least one Ser₃₄₇ allele (*/Ser₃₄₇) were 36.5%, 33.8%, and 34.3% in controls, overweight, and obese subjects, respectively (not significant), and those of the Ser₃₄₇/Ser₃₄₇ genotype were 4.5%, 3.0%, and 2.2%, respectively (not significant). In both men and women, mean BMI and body weight were not significantly different among APOA4 genotypes. There was no evidence of heterogeneity among centers, smoking status, alcohol intake, physical activity, and educational level categories. In men, mean waist girth was lower in Ser₃₄₇/Ser₃₄₇ (92.2 ± 9.4 cm) than in Thr₃₄₇ carriers (95.9 ± 10.9 cm; p = 0.01), and plasma triglycerides levels were lower in Ser₃₄₇ (1.41 ± 1.04 mM) than in Thr₃₄₇/Thr₃₄₇ carriers (1.55 ± 1.23 mM; p = 0.01). Discussion: These results suggest that the APOA4 347Ser allele is not a major risk factor for obesity or overweight.     

A polymorphism in <Emphasis Type="Italic">PTPN2</Emphasis> gene is associated with an earlier onset of type 1 diabetes

The Wellcome Trust Case Control Consortium (WTCCC) genome-wide study found association of PTPN2 with three autoimmune diseases, among them is type 1 diabetes (T1D). This result was confirmed by a follow-up study that pointed to new independent signals within the region. However, both studies were performed in patients with an early-onset T1D. We aimed at replicating the previous results and studying the influence of these polymorphisms in the age at T1D debut. We genotyped 439 T1D Spanish subjects (age at onset, 1 to 65 years) and 861 controls for two PTPN2 single nucleotide polymorphisms (SNPs), rs2542151 and rs478582, and studied the effect of both polymorphisms in age at onset through stratified and continuous analyses. The frequency of rs2542151*G carriers was significantly higher in the early-onset group compared with late-onset patients (p = 0.023) and with controls (OR = 1.61 [1.14–2.26]; p = 0.005). No significant differences were found between controls and late-onset patients. The log-rank chi-square test for the Kaplan–Meier plots (carriers of susceptibility allele vs non carriers) was statistically significant (χ _1df² = 4.485; p = 0.034), yielding an earlier disease debut for G carriers. The analysis of the SNP rs478582 did not reach statistical significance. In summary, we replicate the association detected by the WTCCC and propose that the rs2542151*G allele confers risk to an earlier onset of T1D.     

Polymorphism of alcohol dehydrogenase gene ADH1B in eastern Slavic and Iranian-speaking populations

Frequencies of alleles and genotypes for alcohol dehydrogenase gene ADH1B (arg47his polymorphism), associated with alcohol tolerance/sensitivity, were determined. It was demonstrated that the frequency of allele ADH1B*47his, corresponding to atypical alcohol dehydrogenase variant in Russians, Ukrainians, Iranians, and mountain-dwellers of the Pamirs constituted 3, 7, 24, and 22%, respectively. The frequencies established were consistent with the allele frequency distribution pattern among the populations of Eurasia. Russians and Ukrainians were indistinguishable from other European populations relative to the frequency of allele ADH1B*47his, and consequently, relative to specific features of ethanol metabolic pathways. The data obtained provide refinement of the geographic pattern of ADH1B*47his frequency distribution in Eurasia.     

Genetic polymorphism of <Emphasis Type="Italic">CYP2C19</Emphasis> in a Jordanian population: influence of allele frequencies of <Emphasis Type="Italic">CYP2C19*1</Emphasis> and <Emphasis Type="Italic">CYP2C19*2</Emphasis> on the pharmacokinetic profile of lansoprazole

To relate the pharmacokinetics of orally administered lansoprazole in healthy adult Jordanian men with CYP2C19 polymorphisms and to determine the percentage of CYP2C19 polymorphism in Jordanian population and the allelic frequency of CYP2C19*2 and CYP2C19*3. A total of 78 healthy Jordanian volunteers were included in this study from three different bioequivalence studies, one of these studies which included 26 volunteers was done on lansoprazole. Genotyping for CYP2C19*1, CYP2C19*2, CYP2C19*3 was done for all 78 volunteers, the data of genotyping of all subjects used for screening the frequency of different genotypes and the allelic frequency of different polymorphisms in healthy Jordanian men, the pharmacokinetics and genotyping data for the study of lansoprazole was matched and compared to investigate presence of statistical differences in pharmacokinetic parameters. In Jordanian subjects, the allele frequencies of the CYP2C19*2 and CYP2C19*3 mutation were 0.16 and 0, respectively. The concentration–time curves in the two groups [homozygote extensive metabolizer (homEM, n = 19) and heterozygote extensive metabolizer (homEM, n = 7)] groups were fitted to a non-compartment model. In the homEM and in the hetEM groups, the main kinetic parameters were as follows: T_max (2.1875 ± 0.777) and (2.54 ± 1.87) h, C_max (697.875 ± 335) and (833.58 ± 436.26) mg/l, t_1/2 (1.3 ± 0.43) and (2.38 ± 1.64) h, AUC_(0→∞) were (1,684.9 ± 888) and (3,609.8 ± 318) mg h l⁻¹, respectively. The Jordanian population showed similarities in CYP2C19 allele and genotype distribution pattern with Caucasians and Africans. CYP2C19 allele and poor metabolizer (PM) genotype frequencies in the Jordanian population are distinct from populations’ from East Asia such as Japanese and Koreans. Although lower pharmacokinetic parameters were found in homEM compared to hetEM but there was no significant difference between the two groups (P < 0.05).     

Genetic Demographic Survey of the Gagauz Population of Moldova

The genetic demographic structure of the Gagauz population of Moldova has been described for the first time. Data of interviews and official records have been used to analyze the sex and age structure of the population and marriage relationships, as well as to estimate the effective sizes of the populations of six settlements and selection intensity (according to Crow's formula). The demographic data indicate that social transformations have substantially affected the genetic demographic parameters of the population. The gene exchange rate per generation has been determined (m = 0.0204 in 1972 and m= 0.0309 in 1997). The estimated ratio between the components of Crow's index (I _m < I _f) in the Gagauz population is similar to those for the populations of developed countries with traditionally rural lifestyles. The study of marriage relationships of the Gagauz population has shown that Gagauzes are intensely mixing with Moldovans, Bulgarians, Russians, and Ukrainians.     

Linkage and association of proinflammatory cytokines genes <Emphasis Type="Italic">IL-6, IFNG</Emphasis> and <Emphasis Type="Italic">TNF</Emphasis> with multiple sclerosis

Proinflammatory cytokines interleukin-6 (IL-6), interferon-γ (IFNg) and tumor necrosis factor (TNF) play an important role in the pathogenesis of multiple sclerosis. Based on the published data concerning the effects of the SNPs G(−308)A of TNF, A(+874)T of IFNG, and G(−174)C of IL-6 on the production of these cytokines, we investigated the relation of these polymorphisms with multiple sclerosis. Linkage and association of alleles of these genes with multiple sclerosis were analyzed by transmission disequilibrium test. In a group of 104 nuclear families of Russian ethnicity, the TNF*(−308)A allele was more frequently transmitted from healthy heterozygous parents to affected children (p = 0.01). Linkage/association of IFNG and IL-6 alleles with multiple sclerosis was not detected. Thus, the data obtained indicate that TNF is involved in susceptibility to multiple sclerosis in Russians.