In this investigation associations of gene complexes consisting of seven candidate for coronary atherosclerosis (ACE, AGT, NOS3, APOA1, MTHFR, PLAT, F13) with risk factors for CAD (lipid levels, blood pressure, body mass index (BMI)) were studied in Russian population. 94 male patients with CAD proven by angiography and 131 healthy individuals were involved in the case-control study. We observed a significant contribution of gene combinations (""ensembles""). ACE-MTHFR, ACE-F13, ACE-AGT-MTHFR in the variability of the total cholesterol and LDL-cholesterol levels. The ""Ensembles"" ACE-AGT-MTHFR were associated with variability of three atherogenic risk factors (LDL, BMI, cholesterol total). Two-locus gametic disequilibrium was analysed between gene polymorphisms. NOS3 and ACE, NOS3 and APOA1 were in gametic disequilibrium in the control group. Polymorphic markers of ACE and F13, NOS3 and F13, ACE and PLAT loci were in gametic disequilibrium in the patients. Both approaches (association analysis and gametic disequilibrium) revealed the same gene combinations contributing to the CAD risk factors. NOS3 and APOA1 markers were in gametic disequilibrium in the patients and both of them were associated with LDL. F13 and AGT were associated with systolic and diastolic blood pressure and two-locus gametic disequilibrium between F13 and AGT polymorphisms observed in the patients.

Определяли уровень общего сывороточного интерлейкина-5 и анализировали ассоциацию полиморфизма С-703Т гена IL5 с заболеванием у больных атопической бронхиальной астмой и членов их семей. Наследуемость уровня интерлейкина-5 составила 74.74%. Показана достоверная ассоциация полиморфизма С-703Т гена IL5 с астмой (/>=0.033). Совокупность полученных данных свидетельствует о важной роли полиморфизма гена IL5 в патогенезе заболеваний, характеризующихся выраженным эозинофильным воспалением.

Проведена оценка уровней маркеров воспаления и изучена их взаимосвязь у больных бронхиальной астмой и членов их семей. Результаты свидетельствуют о взаимосвязи эозинофилов, IgE и бронхиальной гиперреактивности в механизмах развития астмы и атопии.

The problem of the presence of imprinted regions on the X-chromosome and the possible influence of the imprinted expression of X-linked genes on the embryonic development in man remains largely unsolved. A comparison of the uniparental inheritance of chromosomes or of their regions having different phenotypic manifestations provides an instrument with which to study the phenomenon of genomic imprinting at the chromosomal level. Assuming that the imprinted inactivation of X-chromosomes is functionally significant for embryonic development, we have studied several polymorphic micro- and minisatellite loci of X-chromosomes in 52 fetuses with karyotype 46.XX, which were spontaneously aborted during the first trimester of pregnancy. The purpose was to determine the contribution of uniparental disomy for the X-chromosome in any disturbances of the embryonic development. We found that inheritance of X-chromosomes was biparental in the studied embryos, suggesting the absence of any significant contribution of the parental origin of the X-chromosome to embryonic mortality occurring between 4 and 12 weeks of development.

Проблема наличия импринтированных участков на Х-хромосоме и возможного влияния импринтированной экспрессии Х-сцепленных генов на эмбриональное развитие человека остается во многом нерешенной. Сравнение однородительского наследования хромосом или их участков, имеющих различные фенотипические проявления, дает инструмент для изучения явления геномного импринтинга на хромосомном уровне. Предполагая, что импринтированная инактивация Х-хромосом функционально значима для эмбрионального развития, мы изучили несколько полиморфных микро- и минисателлитных локусов Х-хромосом у 52 плодов с кариотипом 46.ХХ, самопроизвольно прервавшихся в I триместре беременности. Цель состояла в том, чтобы определить вклад однородительской дисомии по Х-хромосоме в какие-либо нарушения эмбрионального развития. Мы обнаружили, что наследование Х-хромосом было двуродительским у исследованных эмбрионов, что свидетельствует об отсутствии какого-либо значимого вклада родительского происхождения Х-хромосомы в эмбриональную смертность, происходящую между 4 и 12 неделями развития.

The problem of the functioning specificity of sex chromosomes during the early stages of embryogenesis in man and the associated problem of the sex ratio in spontaneous and induced abortions, as well as in newborns, remains open. We have conducted a cytogenetic examination of 342 spontaneous abortions divided into three clinical groups on the basis of the severity of the developmental disturbances of the embryo: spontaneous abortionssensu stricto with a developed embryo without any significant intrauterine delay of development (n=100), nondeveloping pregnancies (n=176), and anembryonic fetuses (n=66). The frequency of chromosomal mutations in these groups was 22.0, 48.3, and 48.5%, respectively. Statistical analysis has demonstrated significant differences between the studied groups in the frequencies of the normal and abnormal karyotypes: the major contributions to these differences were associated with autosomal trisomy, triploidy, and the 46.XY karyotype. The presence of 46.XY may reflect the specific genetic mechanisms of the prenatal mortality of embryos with the normal karyotype, associated with sex and/or with the imprinting of X-chromosomes. The sex ratio in spontaneous abortions with the normal karyotype was as follows: 0.77 for spontaneous abortions with well-developed embryos without any significant intrauterine delay of development; 0.60 for nondeveloping pregnancies; and 0.31 for anembryonic fetuses. An analysis of DNA from the embryos and their parents has demonstrated a low probability of contamination of cell cultures with mother cells as a possible source of the prevalence of embryos with the 46.XX karyotype among spontaneous abortions. Nondeveloping pregnancies and anembryonic fetuses showed statistically significant differences in the sex ratio from the control group consisting of medical abortions (1,11). Differences in the sex ratio were due to an increasingly lower proportion of embryos with karyotype 46.XY (relative to the expected one) among the fetuses with an increased severity of developmental disturbances. The statistical “chances ratio” index also provided evidence that embryos with the 46.XY karyotype had a higher propensity to produce a well-formed fetus as compared with the female embryos. We propose that the expression of genes of the maternal X-chromosome in XY embryos supports a more stable development during early embryogenesis as compared with XX embryos. In the latter case, normal development is coupled with the operation of an additional mechanism for compensation of the dose of X-linked genes. Operation of this mechanism increases the probability of disturbances in female embryos. A higher viability of XY embryos during the early stages of ontogenesis in man appears to explain their underrepresentation in samples of spontaneously aborted embryos and appears to be the major factor responsible for the deviation of the sex ratio from the theoretically expected value.