Dataset Information

Association of VEGFA and IL1? gene polymorphisms with preeclampsia in Sudanese women.

ABSTRACT: BACKGROUND:Preeclampsia can lead to adverse maternal and perinatal outcomes. There are few studies on the genetic factors associated with preeclampsia in Africa in general and in Sudan in specific. METHODS:A case-control study (60 women in each arm) was conducted at Saad Abualila Hospital in Khartoum, Sudan, from March to September 2018. The participants were genotyped for vascular endothelial growth factor A (VEGFA) rs3025039, interleukin 1 beta (IL1?) rs16944, and IL1? rs1143634 by performing polymerase chain reaction-restriction fragment length polymorphism analysis, and the results were confirmed by DNA sequencing. RESULTS:There was no significant difference in the age, parity, body mass index, or other characteristics tested between the preeclampsia group and the control group (60 women in each arm). The rs3025039, rs16944, and rs1143634 genotypes were distributed in accordance with Hardy-Weinberg equilibrium (p > .05). For rs3025039, CT, CT+TT, and the T allele were risk factors for preeclampsia (odds ratio [OR] = 2.4; 95% CI [1.12-5.32]; p = .02; OR = 2.49 [1.17-25.27]; p = .01; OR = 2.05; 95% CI [1.10-3.83]; p = .02, respectively). Regarding rs16944, only the heterozygous genotype CT was associated with preeclampsia (OR = 2.55; 95% CI [1.15-5.56]; p = .01). Regarding rs1143634, CT, CT+TT, and the T allele were risk factors for preeclampsia (OR = 5.28; 95% CI [2.26-12.33]; p < .001; OR = 4.50; 95% CI [2.06-9.81]; p < .001; OR = 2.75; 95% CI [1.48-5.12]; p = .001, respectively). CONCLUSION:Polymorphisms in IL1? and VEGFA were associated with preeclampsia in this setting. Significant associations were observed between preeclampsia and rs3025039, rs16944, and rs1143634.

SUBMITTER: Hamid HM

PROVIDER: S-EPMC7057117 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Association of VEGFA and IL1β gene polymorphisms with preeclampsia in Sudanese women.

Hamid Hameed M HM Abdalla Sana E SE Sidig Mohamed M Adam Ishag I Hamdan Hamdan Z HZ

Molecular genetics & genomic medicine 20200114 3

<h4>Background</h4>Preeclampsia can lead to adverse maternal and perinatal outcomes. There are few studies on the genetic factors associated with preeclampsia in Africa in general and in Sudan in specific.<h4>Methods</h4>A case-control study (60 women in each arm) was conducted at Saad Abualila Hospital in Khartoum, Sudan, from March to September 2018. The participants were genotyped for vascular endothelial growth factor A (VEGFA) rs3025039, interleukin 1 beta (IL1β) rs16944, and IL1β rs1143634 ...[more]

PMID: 31943890

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Project description:BACKGROUND:Leptin receptor gene (LEPR) variants may affect the leptin levels and act as a risk factor for preeclampsia. Two LEPR gene missense variants rs1137101 (c.668A>G) and rs1805094 (c.1968G>C) were investigated in Sudanese women with preeclampsia. METHODS:A matched case-control study (122 women in each arm) was conducted in Saad Abualila Maternity Hospital in Khartoum, Sudan from May to December 2018. The cases were women with preeclampsia and the controls were healthy pregnant women. Genotyping for LEPR gene variants c.668A>G and c.1968G>C was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models (adjusted for age, parity, body mass index and hemoglobin level) were conducted. RESULTS:Genotype frequency of LEPR gene variants c.668A>G and c.1968G>C was in accordance with Hardy-Weinberg equilibrium (P?>?0.05) in the controls. Allele G in LEPRc.668A>G variant was significantly more frequent in the cases compared with the controls [43.4% vs. 10.2%; OR?=?6.44; 95%CI (3.98-10.40); P?<?0.001]. In variant LEPRc.668A>G, genotype AG was the prevalent genotype in the cases compared with the controls, and it was significantly associated with preeclampsia risk [37.7% vs. 15.5%; AOR?=?3.48; 95%CI (1.15-10.54); P?= 0.027]. Likewise, the GG genotype was the second most common genotype in the cases compared with the controls, and was associated with preeclampsia risk [24.6% vs. 2.5%; AOR?=?14.19; 95%CI (1.77-113.76); P?=?0.012]. None of the LEPRc.1968G>C variant genotypes were associated with preeclampsia. The CC genotype was not detected in neither the cases nor the controls. The haplotype A-G 70.1% was the prevalent haplotype in this population, and it significantly protected against preeclampsia [OR?=?0.14; 95%CI (0.09-0.23); P?<?0.001]. However, the haplotype G-G 26.8% was significantly associated with preeclampsia risk [OR?=?6.70; 95%CI (4.16-11.05); P?<?0.001]. Both variants c.668A>G and c.1968G>C were in strong linkage disequilibrium (D'?=?1, r2?=?0.012). CONCLUSIONS:Our data indicate that the rs1137101 (c.668A>G) variant and G-G haplotype may independently associate with the development of preeclampsia.

Project description:BACKGROUND:Preeclampsia is a serious pregnancy-specific syndrome with incompletely understood pathogenesis. Previous study has demonstrated that the decreased CXCR2 in preeclamptic placentas may contribute to the development of preeclampsia. The role of single nucleotide polymorphisms (SNPs) of CXCR2 gene in the pathogenesis of preeclampsia remains largely unexplored. Thus, we aimed to investigate the association between polymorphisms of CXCR2 gene and preeclampsia in Han Chinese women. METHODS:Totally 481 pregnant women, including 243 controls and 238 patients with preeclampsia were recruited. The rs1126579 and rs2230054 polymorphisms in CXCR2 gene were tested using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS:Significantly increased risk of preeclampsia was observed in the rs1126579 CC or TC/CC genotypes when compared with TT genotype (CC vs. TT: odss ratio [OR] = 2.11, 95% confidence interval [CI] = 1.18-3.76, p = 0.039; TC/CC vs. TT: OR = 1.89, 95% CI = 1.29-2.78, p = 0.001). Markedly higher risk of preeclampsia was found to be associated with rs1126579 TC genotype (TC vs. TT/CC: OR = 1.48, 95% CI = 1.04-2.12, p = 0.031). After stratification analysis, the different distribution of TC/CC genotypes was particularly significant in the severe preeclampsia group (OR = 2.15, 95% CI = 1.42-3.24, p < 0.01), the early-onset severe preeclampsia group (OR = 1.97, 95% CI = 1.14-3.42, p = 0.013), and the late-onset severe preeclampsia group (OR = 2.29, 95% CI = 1.39-3.78, p < 0.01). Besides, TC genotype carriers had a 1.55 fold increased risk of severe preeclampsia (95% CI = 1.06-2.27, p = 0.022) and a 1.80 fold increased risk of late onset severe preeclampsia (95% CI = 1.14-2.83, p = 0.01) than those of TT/CC genotype carriers. CONCLUSIONS:Our study suggests a genetic association between rs1126579 polymorphism in CXCR2 gene and increased risk of preeclampsia. These data provide a new clue for future investigation.

Project description:Essential hypertension (EH) is influenced by various environmental and genetic factors. Nitric oxide is important for the functional integrity of the vascular endothelium and is produced in endothelial cells by the enzyme endothelial nitric oxide synthase (eNOS). EH has a strong genetic component, and the NOS3 gene, which encodes eNOS, represents an interesting candidate for contribution to the phenotype. The most clinically relevant polymorphisms in the NOS3 gene are rs1799983 in exon 7 (encoding Glu298Asp), a variable number tandem repeat (VNTR) in intron 4, and rs2070744 (T-786C) in the promoter region. This study aims to investigate the association between these three polymorphisms in the NOS3 gene and EH in Sudanese patients.Hypertensive patients (n?=?157) > 18 years of age with established hypertension from various hospitals in Khartoum, and controls (n?=?85) > 18 years of age and with blood pressure measurements <140/90, were included in this case control study. Genotypes at the NOS3 variants were determined using TaqMan and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analyses. Genotype and allele frequencies were compared between the two groups by ?2 analysis, and differences were expressed as odds ratios with 95% confidence intervals (CIs). P values <0.05 were considered statistically significant.The rs2070744 polymorphism in NOS3 was found to be associated with EH in the Sudanese population as the patients group had higher frequency of CC genotype compared with the controls (6.6% vs 6.1%, p?=?0.02). Considering a dominant inheritance model, the frequency of TC + CC genotypes in patients was significantly higher than that in the control subjects (52.6% vs 34.1%, respectively; p < 0.01), with an odds ratio (95% CI) of 2.14 (1.23-3.74). In addition, the C allele was more frequent in the patients than the control group (29.6% vs 20%, p?=?0.03, OR?=?1.84 (1.15-2.93)). The c allele of intron 4 VNTR was reported in >1% of the Sudanese population under study.The results of this study indicated that the rs2070744 polymorphism in NOS3 may be a genetic susceptibility factor for EH in the Sudanese population. The c allele of intron 4 VNTR is not rare in the Sudanese population.

Dataset Information

Association of VEGFA and IL1? gene polymorphisms with preeclampsia in Sudanese women.

Publications

Association of VEGFA and IL1β gene polymorphisms with preeclampsia in Sudanese women.

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