The association of Q472H variant in the KDR gene with recurrent pregnancy loss in Southern Iran: A case-control study

Background: Recurrent spontaneous abortion (RSA) often remains unclear and can be burden for the patient and time consuming for clinician. RSA may initiates from a genetic or non-genetic factors. It is well known that the quality of placental circulation is critical for implantation and embryo development. Because of angiogenic effects of VEGF–KDR pathway on placenta, the genes involved in this pathway (the KDR or VEGFR genes) are thought to be linked with RSA. Objective: The aim of this study was to investigate the relationship between Gln472His (A/T) polymorphism of the KDR gene with RSAs in southern Iran. Materials and Methods: In this case-control study, 50 aborted embryonic tissue obtained from fetuses and 50 umbilical cord blood of newborn babies were studied. Fetal sample from mothers with history of at least two consecutive miscarriages and controls from mothers who had at least one full-term infants born were taken. Genomic DNA was extracted by using PureLink genomic DNA kit (Life Technologies, CA). The Rotor-Gene Q real-Time PCR machine and High-resolution melting curve analysis (HRM) technique were used for genotyping. Results: Based on the AA genotype as reference, it is shown that the T allele (OR = 2.447, 95% CI = 1.095–5.468, p = 0.029) as well as AT heterozygote genotype was significantly associated with an increased risk of miscarriage (OR = 2.824, 95% CI = 1.210-6.673, p = 0.016). Conclusion: A positive correlation between Q472H polymorphism of the KDR gene and RSA may be the cause in southern Iran

Role of the 820 A/G variant in the IGF-2 gene and recurrent spontaneous abortion in southern Iran: A cross-sectional study

Background: Insulin-like growth factor-2 (IGF-2) is a polypeptide growth factor and one of the first genes expressed prior to the implantation of the embryo, with its highest expression in the placental cells. Its activity strongly depends on the genomic imprinting, and the result of the loss of genetic imprinting is the termination of the early stages of embryonic development, which can lead to recurrent spontaneous abortion. Objective: This cross-sectional study aimed to investigate the role of 820A/G variant of the IGF-2 gene and the probability to recurrent spontaneous abortion (RSA) in southern Iran. Materials and Methods: In this study, 50 aborted fetuses tissue for the study group and blood samples umbilical-cord from newborns as control group (n = 50) were collected from Shiraz-Iran (2017). The genotyping of the target point in the IGF-2 gene was performed by Real-time Polymerase Chain Reaction and analyzed through highresolution melting (HRM) curve. Results: Based on the collected data (AA genotype = reference), allele “A” frequency in aborted fetus was 51% and control 68% as well as allele G 49% and 32%, respectively. Moreover, 27 aborted embryos (54%) were heterozygous (A/G) (OR = 3.274, 95% CI = 1.015-10.561, p = 0.04), while 18 cases (36%) in control sample showed heterozygosity. Considering the phenotypic status, the G allele had a dominant effect on the incidence of RSA (p = 0.008, OR = 3.167). Conclusion: Based on the present study, the risk of abortion due to loss of heterozygosity or quantitative decline of the IGF-2 is about three-fold in the southern Iran. Key words: Variant, IGF-2, Spontaneous abortion, Genomic imprinting, Gene expression

Role of SIRT-1 rs7895833 polymorphism in susceptibility to polycystic ovary syndrome

Introduction: Sirtuin 1 is a protein deacetylase that plays an important role in many cellular processes. The serum sirtuin 1 levels are higher in the polycystic ovary syndrome (PCOS) patients than the healthy subjects. The aim of this study was to assess the role of SIRT-1 rs7895833 polymorphism in the susceptibility of PCOS. Methods: This case-control study was done on 456 Iranian women from March to February 2015. Blood samples were collected from 274 women with PCOS and 182 age matched (±5) healthy women at Shiraz Ghadir Mother and Child Hospital. After DNA extraction, SIRT1 rs7895833 genotype determination was done by Tetra-ARMS PCR. Data analysis was performed by SPSS version 18. Results: In the dominant model for G allele (AG+GG vs. AA), AG+GG genotypes in SIRT1 rs7895833 gene polymorphism was associated with the increased risk of PCOS (OR: 2.01, %95CI:1.32-3.24, P=0.002). Moreover, there was a significant association between the G allele and PCOS (OR: 1.45, %95CI:1.10-1.91, P=0.008). Conclusion: The results showed a possible association between SIRT1 rs7895833 gene polymorphism and susceptibility to PCOS

The Association of Q472H Variant in the KDR Gene with Recurrent Pregnancy Loss in Southern Iran: A Case-control Study

Background: Recurrent spontaneous abortion (RSA) often remains unclear and can be burden for the patient and time consuming for clinician. RSA may initiates from a genetic or non-genetic factors. It is well known that the quality of placental circulation is critical for implantation and embryo development. Because of angiogenic effects of VEGF–KDR pathway on placenta, the genes involved in this pathway (the KDR or VEGFR genes) are thought to be linked with RSA. Objective: The aim of this study was to investigate the relationship between Gln472His (A/T) polymorphism of the KDR gene with RSAs in southern Iran. Materials and Methods: In this case-control study, 50 aborted embryonic tissue obtained from fetuses and 50 umbilical cord blood of newborn babies were studied. Fetal sample from mothers with history of at least two consecutive miscarriages and controls from mothers who had at least one full-term infants born were taken. Genomic DNA was extracted by using PureLink genomic DNA kit (Life Technologies, CA). The Rotor-Gene Q real-Time PCR machine and High-resolution melting curve analysis (HRM) technique were used for genotyping. Results: Based on the AA genotype as reference, it is shown that the T allele (OR = 2.447, 95% CI = 1.095–5.468, p = 0.029) as well as AT heterozygote genotype was significantly associated with an increased risk of miscarriage (OR = 2.824, 95% CI = 1.210-6.673, p = 0.016). Conclusion: A positive correlation between Q472H polymorphism of the KDR gene and RSA may be the cause in southern Iran

Evaluation the frequency of factor V Leiden mutation in pregnant women with preeclampsia syndrome in an Iranian population

Background: Role of genetic factors in etiology of preeclampsia is not confirmed yet.Objective: Gene defect frequency varies in different geographic areas as well as ethnic groups. In this study, the role of factor V Leiden mutation in the pathogenesis of preeclampsia syndrome among the pregnant population of northern shore of Persian Gulf in Iran, were considered.Materials and Methods: Between Jan. 2008 and Dec. 2009, in a nested case control study, pregnant women with preeclampsia (N=198) as cases and healthy (N=201) as controls were enrolled in the study. DNA were extracted from 10 CC peripheral blood and analyzed for presence of factor V Leiden mutation in these subjects. The maternal and neonatal outcomes of pregnancy according to the distribution of factor V Leiden were also compared among cases.Results: In total, 17(8.6%) of cases and 2(1%) of controls showed the factor V Leiden mutation. The incidence of factor V Leiden was typically higher in preeclamptic women than control group (OR: 9.34 %95 CI: 2.12-41.01). There was no difference in incidence rate of preterm delivery< 37 weeks (OR: 1.23 %95 CI: 0.38-4.02), very early preterm delivery<32 weeks (OR: 1.00 %95 CI: 0.12-8.46), intra uterine fetal growth restriction (IUGR) (OR: 1.32 %95 CI: 0.15-11.30 ),and the rate of cesarean section (OR: 0.88 %95 CI: 0.29-2.62 ) among cases based on the prevalence of factor V Leiden mutation.Conclusion: The pregnant women with factor V Leiden mutation are prone for preeclampsia syndrome during pregnancy, but this risk factor was not correlated to pregnancy complications in the studied wome

Molecular Basis of Hb H Disease in Southwest Iran

International audienceAlthough alpha(0)-thalassemia (thal) defects are not very frequent in the Iranian population, Hb H disease does occur in the country. We have analyzed the alpha gene cluster of 13 patients showing the presence of Hb H to establish the molecular background of this disease in southwest Iran (Shiraz and Hormozgan provinces). Using gap-polymerase chain reaction (gap-PCR) and direct DNA sequencing we have found the ―(MED-I) deletion, the polyadenylation signal (poly A) mutations alpha(T-Saudi)alpha and alpha(T-Turkish)alpha, and Hb Constant Spring (Hb CS) in association with the common -alpha(3.7) deletion. This study has revealed that: 1) at least six genotypes are responsible for Hb H disease in the area: -alpha(3.7)/ ―(MED-I); -alpha(3.7)/alpha(T-Saudi)alpha; alpha(T-Saudi)alpha/alpha(T-Saudi)alpha; alpha(CS)alpha/―(MED-I); ―(MED-I)/alpha(T-Turkish)alpha; and the atypical forms of Hb H disease -alpha(3.7)/alpha(CS)alpha. 2) The molecular background of Hb H disease in the southwest area of Iran is more similar to the Mediterranean type than to the Southeast Asian. 3) Hb Bart's hydrops fetalis syndrome and mild, intermediate or severe postnatal Hb H disease conditions can be expected, but at a relatively low incidence. 4) The diagnostic flowchart for patients with microcytic hypochromic anemia should include iron deficiency, beta-thal, alpha(+)- and alpha(0)-thal analyses