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MMP-2 and MMP-9 Polymorphisms and Preeclampsia Risk in Tunisian Arabs: A Case-Control Study.

ABSTRACT: The abnormal production of matrix metalloproteinases (MMPs), especially MMP-9 and MMP-2, plays a pivotal role in hypertensive disorders of pregnancy, and as such, can influence the development of preeclampsia. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 and MMP-2 genes, which modify MMP-9 and MMP-2 expression. We investigated the association of MMP-9 polymorphism rs3918242 (-1562 C>T) and MMP-2 polymorphism rs2285053 (-735 C>T) with the risk of preeclampsia. This case-control study was conducted on 345 women with preeclampsia and 281 age-matched women with normal pregnancies from Tunisian hospitals. Genomic DNA was extracted from whole blood collected at delivery. Genotypes for -1562 C>T and -735 C>T polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An increased frequency of heterozygous MMP-9 -1562 C/T genotype carriers was observed in women with preeclampsia compared to healthy controls (p = 0.03). In contrast, the MMP-2 -735 C>T polymorphism was not significantly different regarding frequency distribution of the allele and genotype between healthy pregnant women and women with preeclampsia. Our study suggests that the MMP-9 -1562 C/T variant, associated with high MMP-9 production, could be a genetic risk factor for preeclampsia in Tunisian women.

SUBMITTER: Gannoun MBA

PROVIDER: S-EPMC8234886 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Risk factors for preeclampsia in women from Colombia: a case-control study.

Project description:BACKGROUND: Preeclampsia (PE) is a multi-causal disease characterized by the development of hypertension and proteinuria in the second half of pregnancy. Multiple risk factors have been associated with the development of PE. Moreover, it is known that these risk factors vary between populations from developed and developing countries. The aim of this study is to identify which risk factors are associated with the development of preeclampsia (PE) among Colombian women. METHODS: A multi-centre case-control study was conducted between September 2006 and July 2009 in six Colombian cities. Cases included women with PE (n = 201); controls were aged-matched pregnant women (n = 201) without cardiovascular or endocrine diseases for a case-control ratio of 1:1. A complete medical chart, physical examination and biochemical analysis were completed before delivery. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of potential risk factors associated with PE. RESULTS: The presence of factors present in the metabolic syndrome cluster such as body mass index >31 Kg/m2 (OR = 2.18; 1.14-4.14 95% CI), high-density lipoprotein <1.24 mmol/L (OR = 2.42; 1.53-3.84 95% CI), triglycerides >3.24 mmol/L (OR = 1.60; 1.04-2.48 95% CI) and glycemia >4.9 mmol/L (OR = 2.66; 1.47-4.81 95%CI) as well as being primigravidae (OR = 1.71; 1.07-2.73 95% CI) were associated with the development of PE, after adjusting for other variables. CONCLUSION: Factors present in the cluster of metabolic syndrome and primigravidity were associated with a greater risk of PE among Colombian women. Understanding the role of this cluster of risk factors in the development of PE is of crucial importance to prevent PE and remains to be determined.

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Renin-angiotensin-aldosterone system gene polymorphisms in gestational hypertension and preeclampsia: A case-control gene-association study.

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| S-EPMC5133626 | biostudies-literature

Association between polymorphisms rs2228001 and rs2228000 in XPC and genetic susceptibility to preeclampsia: a case control study.

Project description:BackgroundXeroderma pigmentosum complementation group C (XPC) is a DNA damage recognition protein that plays an important role in nucleotide excision repair and can reduce oxidative stress, which may be involved in the development of preeclampsia (PE). Therefore, the aim of this study was to explore whether XPC polymorphisms were relevant to the genetic susceptibility to PE in Chinese Han women.MethodA total of 1276 healthy pregnant women were included as the control group and 958 pregnant women with PE as the case group. DNA was extracted from peripheral blood samples to perform genotyping of loci rs2228001 and rs2228000 in XPC through real-time quantitative polymerase chain reaction (PCR). The relationship between XPC and susceptibility to PE was evaluated by comparing the genotypic and allelic frequencies between the two groups of pregnant women.ResultsPolymorphism of rs2228000 may be associated with PE risk and allele T may play a protective role (genotype, χ2 = 38.961, P < 0.001 and allele χ2 = 21.746 P < 0.001, odds ratio (OR) = 0.885, 95% confidence interval (CI) = 0.840-0.932). No significant difference was found between the two groups in rs2228001,(genotype χ2 = 3.148, P = 0.207 and allele χ2 = 0.59, P = 0.442, OR = 1.017, 95% CI = 0.974-1.062). When the frequencies of genotypes and alleles for early- and late-onset PE, mild PE and severe PE were compared with those of controls, the results were consistent with the large clinical sample.ConclusionOur data suggest that the genetic variant rs2228000 in XPC may be associated with PE risk in Chinese Han women, and that pregnant women with the TT genotype have a reduced risk of PE. Further investigations are needed to confirm these findings in other regions or larger prospective populations.

| S-EPMC8607566 | biostudies-literature

Exploration of CYP21A2 and CYP17A1 polymorphisms and preeclampsia risk among Chinese Han population: a large-scale case-control study based on 5021 subjects.

Project description:BackgroundSeveral genome-wide association studies have identified single-nucleotide polymorphisms (SNPs), such as rs4409766, rs1004467, and rs3824755 in CYP17A1 and rs2021783 in CYP21A2, as new hypertension susceptibility genetic variants in the Chinese population. This study aimed to look into the relationship between preeclampsia (PE) and these SNPs in Chinese Han women.MethodsOverall, 5021 unrelated pregnant women were recruited, including 2002 patients with PE and 3019 normal healthy controls. The real-time PCR (TaqMan) method was applied to genotype these four polymorphisms.ResultsA statistically obvious difference in the allelic frequencies was observed in CYP21A2 rs2021783 between cases and controls (χ2 = 7.201, Pc = 0.028 by allele), and the T allele was associated with the occurrence and development of PE (OR = 1.151, 95% CI 1.039-1.275). We also found a significant association between rs2021783 and the development of early-onset PE (Pc = 0.008 by genotype, Pc = 0.004 by allele). For rs1004467 and rs3824755, the distribution of allelic frequencies differed markedly between mild PE and control groups (χ2 = 6.843, Pc = 0.036; χ2 = 6.869, Pc = 0.036), and patients with the TT genotype of rs1004467 were less easy to develop mild PE than were those carrying the CT or CC genotype (χ2 = 7.002, Pc = 0.032, OR = 1.306, 95% CI 1.071-1.593). The GG genotype of rs3824755 appeared to a protective effect on the occurrence of mild PE (OR = 0.766, 95% CI 0.629-0.934).ConclusionsCYP21A2 rs2021783 appears to be closely related to PE susceptibility, and CYP17A1 rs1004467 and rs3824755 seem to be closely associated with mild PE in Han women.

| S-EPMC7517682 | biostudies-literature

IKZF1 genetic variants rs4132601 and rs11978267 and acute lymphoblastic leukemia risk in Tunisian children: a case-control study.

Project description:BackgroundAssociations between IKZF1 gene variants and Acute Lymphoblastic Leukemia (ALL) was recently reported. We examined whether the common IKZF1 polymorphisms rs4132601 T/G and rs111978267 A/G are associated with ALL among a Tunisian pediatric cohort.MethodsThis case-control study involved 170 patients with ALL and 150 control subjects. SNP genotyping was performed by TaqMan® SNP Genotyping Assay.ResultsThe minor allele G of IKZF1 gene polymorphism rs4132601 T/G was significantly higher in ALL cases than in control subjects (P = 0.029), with 1.54-fold increased risk of ALL. The association of rs4132601 with ALL was seen under co-dominant (P = 0.009), recessive (P = 0.006), and additive (P = 0.027) genetic models, of which the co-dominant (P = 0.027) and recessive (P = 0.027) association remained significant after adjusting for covariates, and False Discovery Rate correction. In contrast, no association was noted for rs111978267 variant. Two-locus (rs4132601-rs11978267) IKZF1 haplotype analysis demonstrated association of GA (P = 0.053), with increased ALL risk [OR (95% CI) = 1.58 (1.00-2.51)], which remained significant after controlling for key covariates [aP = 0.046; aOR (95% CI) = 1.61 (1.01-2.57)].ConclusionWe demonstrated the association of IKZF1 polymorphism rs4132601 T/G with increased risk of ALL among Tunisian pediatric cohort, with altered phenotypic changes among ALL patients.

| S-EPMC6788013 | biostudies-literature

Contrasting association of Leptin receptor polymorphisms and haplotypes with polycystic ovary syndrome in Bahraini and Tunisian women: a case-control study.

Project description:The present study examined the contribution of ethnicity to the association of leptin receptor gene (LEPR) gene variants with polycystic ovary syndrome (PCOS) in Tunisian and Bahraini Arabic-speaking women. Subjects consisted of 320 women with PCOS, and 446 eumenorrhic women from Tunisia, and 242 women with PCOS and 238 controls from Bahrain. Genotyping of (exonic) rs1137100 and rs1137101 and (intronic) rs2025804 LEPR variants was done by allelic exclusion. The minor allele frequencies (MAFs) of rs1137100 and rs1137101 were significantly different between PCOS cases and control women from Bahrain but not Tunisia, and LEPR rs1137101 was associated with increased PCOS susceptibility only in Bahraini subjects. Furthermore, rs1137100 was associated with decreased PCOS risk among Bahrainis under codominant and recessive models; rs1137100 was negatively associated with PCOS in Tunisians after controlling for testosterone. In addition, rs2025804 was associated with increased PCOS risk among Tunisian but not Bahraini women, after adjusting for key covariates. Negative correlation was seen between rs1137101 and triglycerides in Tunisians, while homeostasis model assessment of insulin resistance (HOMA-IR) and insulin correlated with rs2025804 and rs1137101 among Bahraini subjects, and rs1137101 correlated with estradiol and prolactin. Taking TAG haplotype as common, positive association of TAA and negative association of TGG haplotype with PCOS was seen among Bahraini women; no three-locus PCOS-associated haplotypes were found in Tunisians. The present study is the first to demonstrate the contribution of ethnicity to the association of LEPR gene variants with PCOS, thereby highlighting the significance of controlling for ethnicity in gene association investigations.

| S-EPMC7789794 | biostudies-literature

Physical Activity During Pregnancy and Subsequent Risk of Preeclampsia and Gestational Hypertension: A Case Control Study.

Project description:ObjectivePhysical activity (PA) is hypothesized to reduce the risk of preeclampsia, but few epidemiologic studies have simultaneously evaluated leisure time PA (LTPA), sedentary activity, occupational activity, and non-occupational, non-leisure time PA. Thus, we assessed the independent and combined effects of these different types of PA during pregnancy on preeclampsia and gestational hypertension risk.MethodsPreeclamptic (n = 258), gestational hypertensive (n = 233), and normotensive (n = 182) women identified from Iowa live birth records (2002-2005) were participants in Study of Pregnancy Hypertension in Iowa. Disease status was verified by medical chart review. All PA exposures were self-reported. Multinomial logistic regression was used to test for associations between various PA types and risk for preeclampsia or gestational hypertension.ResultsAfter adjusting for prepregnancy BMI, increasing levels of LTPA were associated with a reduced risk of preeclampsia (trend, p = 0.02). Additionally, increasing amount of time spent active each day was associated with decreasing risks for preeclampsia (adjusted, trend; p = 0.03). Increasing amount of time spent sitting per day was associated with an increasing risk of preeclampsia (adjusted, trend; p = 0.10). Women whose activity averaged >8.25 h per day were at a significantly reduced risk of preeclampsia relative to women active <4.2 h per day (adjusted OR 0.58, 95 % CI 0.36, 0.95). Most analyses evaluating the risk of gestational hypertension yielded null results or results that trended in the direction opposite of the preeclampsia results.ConclusionConsistent with previous studies, these data suggest increasing PA during pregnancy may reduce preeclampsia risk while increasing levels of sedentary activity may increase disease risk.

| S-EPMC5538351 | biostudies-literature

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