RESUMEN
PURPOSE: The role of genetic polymorphisms in the pathogenesis of recurrent pregnancy loss (RPL) has been studied intensively. Complex diseases, including miscarriage, are believed to have a polygenic basis, and gene-gene interactions can play a significant role in the etiology of the disease. This study was conducted to investigate the association of gene-gene interactions with angiogenesis, endothelial dysfunction-related gene polymorphisms, and RPL. METHODS: A case-control study was conducted with 253 unrelated RPL patients with 2 or more spontaneous pregnancy losses and 339 healthy women with no history of pregnancy complications. Genotyping of single-nucleotide polymorphisms (SNPs) was performed using real-time polymerase chain reaction (real-time PCR), restriction fragment length polymorphism (RFLP), or allele-specific polymerase chain reaction methods. RESULTS: The genotypes 677TT of the MTHFR gene, 936TT, 936CT, and 634CC, 634GC of the VEGF gene, and allele 894T of the NOS3 gene were associated with a predisposition to RPL in the Russian population. A significant role of additive and epistatic effects in the gene-gene interactions of the SNPs of SERPINE-1, ACE, NOS3, MTHFR, and VEGF genes in RPL was demonstrated. CONCLUSIONS: The results showed that gene-gene interactions are important for RPL susceptibility. Additionally, analysis of the genotype combinations of several allelic variants provides more information on RPL risk than analysis of independent polymorphic markers.
Asunto(s)
Aborto Espontáneo/genética , Epistasis Genética/genética , Predisposición Genética a la Enfermedad , Trombofilia/genética , Aborto Espontáneo/fisiopatología , Adulto , Alelos , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo de Longitud del Fragmento de Restricción/genética , Polimorfismo de Nucleótido Simple/genética , Embarazo , Factores de Riesgo , Trombofilia/fisiopatología , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Allele frequencies and genetic diversity in the population of Teleuts were assessed by the Alu repeat polymorphism at eight autosomal loci (ACE, APOA1, PLAT, F13, PV92, A25, CD4, Dl). For comparison, the study included previously obtained data on the Alu polymorphism in 19 indigenous populations of Siberia. On the dendrogram of genetic distances, the Teleut population is located in the cluster of Siberian ethnic groups, which are similar in origin, geography, and cultural traditions.
Asunto(s)
Elementos Alu/genética , Etnicidad/genética , Variación Genética , Polimorfismo Genético , Frecuencia de los Genes , Humanos , SiberiaRESUMEN
The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95% CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC, which is associated with MD, and haplotype GTCCTT, which was observed only in Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283) compared with other examined populations was noted. An analysis of pairwise genetic relationships between populations revealed their significant differentiation for all the examined loci. In addition, a low level of differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which was related to the high subdivision of the northern Eurasian population (F(ST) = 11.83%), was observed.