Evaluation of factor v g1691a, factor II g20210a, mthfr c677t and factor v h1299r mutations in women with recurrent pregnancy loss

Tekrarlayan gebelik kaybı, birbirini izleyen en az iki ya da daha fazla gebeliğin 20. gebelik haftasından önce spontan sonlanması olarak tanımlanmaktadır. Tekrarlayan gebelik kayıplarının etiyolojisinde genetik faktörler, %20 oranında rol oynamaktadır. Bu faktörler arasında kromozomal anomaliler, tek gen hastalıkları, tromboza yatkınlık genlerindeki mutasyonlar ve multifaktöriyel değişiklikler bulunmaktadır. Tekrarlayan gebelik kayıpları görülen ailelerde trombofili insidansı %60 oranında görülebilmektedir. Maternal koagülasyon faktörlerindeki mutasyonlar, hemostatik sistemde bozulmalara neden olmakta ve plasental mikrosirkülasyon da tromboza yol açarak abortusla sonuçlanabilmektedir. Çalışmamızda 2013-2018 yılları arasında Afyonkarahisar Sağlık Bilimleri Üniversitesi Tıp Fakültesi Tıbbi Genetik Anabilim Dalı polikliniğine tekrarlayan gebelik kaybı endikasyonuyla başvuran 215 vakada ve 40 kontrolde, Faktör V G1691A, Faktör II G20210A, MTHFR C677T ve Faktör V H1299R mutasyonlarının dağılımı incelenmiştir. Çalışma sonuçlarımıza göre, Faktör V G1691A, Faktör II G20210A, MTHFR C677T ve Faktör V H1299R mutasyonları açısından vaka ve kontrol grubu arasında fark bulunmamıştır (p>0.05). Faktör V geni G1691A polimorfizmi genotip dağılımı, vaka grubunda %12,6 GA heterezigot ve kontrol grubunda %90,0 GG homozigot normal genotip en yüksek oranda saptanmıştır. Faktör II geni G20210A polimorfizmi genotip dağılımı, vaka grubu ve kontrol grubunda sırasıyla %94,5 ve %97,5 GG homozigot normal genotip en yüksek oranda belirlenmiştir. MTHFR geni C677T polimorfizmi genotip dağılımı, vaka grubunda %43,7 CC homozigot normal ve kontrol grubunda %40,0 CT heterezigot genotip en yüksek oranda gözlenmiştir. Faktör V geni H1299R polimorfizmi genotip dağılımı, vaka grubunda %87,4 AA homozigot normal ve kontrol grubunda %80 AA heterezigot genotip en yüksek oranda gözlenmiştir. Faktör V geni G1691A polimorfizmi risk aleli olan A alel sıklığı, vaka grubunda %6,8 ve kontrol grubunda %5,0 oranında belirlenmiştir. Faktör II geni G20210A polimorfizmi risk aleli olan A alel sıklığı, vakalarda %3,0 ve kontrolde %1,3 oranında belirlenmiştir. MTHFR geni C677T polimorfizmi risk aleli olan T alel sıklığı, vaka grubunda %35,9 ve kontrol grubunda %42,5 oranında belirlenmiştir. Faktör V geni H1299R polimorfizmi risk aleli olan G alel sıklığı, vaka grubunda %6,5 ve kontrol grubunda %16,6 oranında belirlenmiştir. Vaka grubunun %60,46’sında 2 gebelik kaybı belirlenmiştir. Çalışma sonuçlarımız değerlendirildiğinde Faktör V G1691A, Faktör II G20210A, MTHFR C677T ve Faktör V H1299R mutasyonları ile tekrarlayan gebelik kayıpları arasında ilişki belirlenmemiştir.Recurrent pregnancy loss is defined as the spontaneous termination of at least two or more consecutive pregnancies before 20 weeks of gestation. Genetic factors play a role in the etiology of recurrent pregnancy loss at a rate of 20%. These factors include chromosomal abnormalities, single gene diseases, mutations in thrombosis susceptibility genes, and multifactorial changes. The incidence of thrombophilia can be seen at a rate of 60% in families with recurrent pregnancy loss. Mutations in maternal coagulation factors cause disruptions in the hemostatic system, and placental microcirculation can also lead to thrombosis, resulting in abortion. In our study, the distribution of Factor V G1691A, Factor II G20210A, MTHFR C677T and Factor V H1299R mutations in 215 cases and 40 control groups who applied to Afyonkarahisar Health Sciences University Faculty of Medicine Medical Genetics Department outpatient clinic with the indication of recurrent pregnancy loss between 2013 and 2018 were investigated. According to our study results, there was no difference between the case and control groups in terms of Factor V G1691A, Factor II G20210A, MTHFR C677T and Factor V H1299R mutations (p>0.05). Factor V gene G1691A polymorphism genotype distribution was found with the highest rate of 12.6% GA heterozygous in the case group and 90.0% GG homozygous normal genotype in the control group. Factor II gene G20210A polymorphism genotype distribution, 94.5% and 97.5% GG homozygous normal genotype was determined at the highest rate in the case group and control group, respectively. Genotype distribution of MTHFR gene C677T polymorphism, 43.7% CC homozygous normal in the case group and 40.0% CT heterozygous genotype in the control group were observed with the highest rate. Factor V gene H1299R polymorphism genotype distribution was observed with the highest rate of 87.4% AA homozygous normal in the case group and 80% AA heterozygous genotype in the control group. The frequency of A allele, which is the risk allele for factor V gene G1691A polymorphism, was determined as 6.8% in cases and 5.0% in controls. The frequency of A allele, which is the risk allele for factor II gene G20210A polymorphism, was determined as 3.0% in the case group and 1.3% in the control group. The frequency of T allele, which is the risk allele for MTHFR gene C677T polymorphism, was determined as 35.9% in case group and 42.5% in the control group. The frequency of the G allele, which is the risk allele for the factor V gene H1299R polymorphism, was determined as 6.5% in the case group and 16.6% in the control group. In 60.46% of the cases, 2 pregnancy losses were determined. When our study results were evaluated, no relationship was found between Factor V G1691A, Factor II G20210A, MTHFR C677T and Factor V H1299R mutations and recurrent pregnancy losses

Effect of gene polymorphisms in transmembrane protein 18 (TMEM18) and neuronal growth regulator 1 (NEGR1) on body mass index in obese subjects

Obesity is a complex disorder with nearly epidemic proportions in many parts of the world. Genome-wide association studies have demonstrated high heritability for obesity and body mass, with associations of certain candidate genes and their variations with respect to race, geographical location/country of origin. However, the functional mechanisms and different ethnic data of these loci are still poorly understood. In this case-control study, we investigated two single nucleotide polymorphisms, rs2815752 in the neuronal growth regulator 1 (NEGR1) gene and rs6548238 in the transmembrane protein 18 (TMEM18) gene, for association in a group of obese residents of Afyonkarahisar province (Turkey). Polymorphisms were genotyped in 172 obese subjects and 77 healthy controls. The results showed no significant differences between the obese subjects and the controls in terms of the allele and genotype frequencies of the NEGR1 gene rs2815752 and the TMEM18 gene rs6548238 polymorphisms. There were no significant associations of the rs2815752 polymorphism in obese subjects and controls with regard to anthropometric measurements and body composition parameters. However, several significant associations were found for the rs6548238 polymorphism with regard to anthropometric measurements and body composition. Consequently, there were no significant differences between the genotype and allele frequencies of NEGR1 gene rs2815752 and TMEM18 gene rs6548238 polymorphisms in the obese group and the controls. There were significant associations for the rs6548238 polymorphism, but not the rs2815752 polymorphism, with the anthropometric measurements and body composition parameters in the group of obese subjects

Relationship between expression levels of TDRD7 and CRYBB3 and development of age-related cortico-nuclear cataracts

Abstract Background The human lens develops age-related cataracts (ARCs) because of the complicated effects of aging and stressful conditions. Under conditions involving oxidative stress, cells form stress granules (SGs). TDRD7 has been identified as an RNA granule component and an important component of SGs. TDRD7 plays a role in the post-transcriptional expression of genes, such as the crystallin gene CRYBB3. Therefore, the present study investigated TDRD7 and CRYBB3 mRNA expressions in relation to age-related cortico-nuclear cataracts. Methods Quantitative real-time PCR was used to determine the expression levels of TDRD7 and CRYBB3 in 52 patients with ARC and 52 healthy controls. Anterior lens capsules and peripheral blood samples from patients with ARC were included in the patient group, and peripheral blood samples from healthy subjects and human lens epithelial cells (HLE-B3) were included in the control group. Gene expression levels in the different age groups were compared. Correlation analysis was used to assess the gene expression levels and age. Results The expression of TDRD7 and CRYBB3 was significantly up-regulated (P < 0.0001) in anterior lens capsules compared to that in HLE-B3 cells. Similarly, the expression of TDRD7 (P = 0.0004) and CRYBB3 (P < 0.0001) was higher in the peripheral blood samples of patients with ARC than in those of healthy subjects. Significant upregulation (P < 0.05) was observed in the 71–81-year age group of patients. No correlation was found between gene expression levels and age. Conclusion Significantly higher expression levels of TDRD7 and CRYBB3 in patients with ARC than in controls suggest that TDRD7 and CRYBB3 are associated with the development of age-related cortico-nuclear cataracts and the aging process under chronic stress

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease