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A fetal variant in the GCM1 gene is associated with pregnancy induced hypertension in a predominantly hispanic population.

ABSTRACT: The aim of the study was to determine whether polymorphism in the GCM1 gene is associated with pregnancy induced hypertension (PIH) in a case-control study of mother-baby dyads. Predominantly Hispanic women, ages 15-45, with (n=136) and without (n=169) PIH were recruited. We genotyped four polymorphisms in the GCM1 gene and examined the association with PIH using both logistic regression and likelihood expectation maximization (LEM) to adjust for intra-familial correlation between genotypes. Maternal genotype was not associated with PIH for any polymorphisms examined. Fetal genotype, however, was associated with maternal risk of PIH. Mothers carrying a fetus with ?1 copy of the minor (C) allele for rs9349655 were less likely to develop PIH than women carrying a fetus with the GG genotype (parity-adjusted OR=0.44, 95% Cl: 0.21, 0.94). The trend of decreasing risk with increasing C alleles was also statistically significant (OR(trend)=0.41 95% Cl: 0.20, 0.85). The minor alleles for the other three SNPs also appear to be associated with protection. Multilocus analyses of fetal genotypes showed that the protective effect of carrying minor alleles at rs9349655 and rs13200319 (non-significant) remained unchanged when adjusting for genotypes at the other loci. However, the apparent (non-significant) effect of rs2816345 and rs2518573 disappeared when adjusting for rs9349655. In conclusion, we found that a fetal GCM1 polymorphism is significantly associated with PIH in a predominantly Hispanic population. These results suggest that GCM1 may represent a fetal-effect gene, where risk to the mother is conferred only through carriage by the fetus.

SUBMITTER: Wilson ML

PROVIDER: S-EPMC3166147 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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A fetal variant in the GCM1 gene is associated with pregnancy induced hypertension in a predominantly hispanic population.

Wilson Melissa L ML Brueggmann Doerthe D Desmond Daniel H DH Mandeville John E JE Goodwin T Murphy TM Ingles Sue Ann SA

International journal of molecular epidemiology and genetics 20110505 3

The aim of the study was to determine whether polymorphism in the GCM1 gene is associated with pregnancy induced hypertension (PIH) in a case-control study of mother-baby dyads. Predominantly Hispanic women, ages 15-45, with (n=136) and without (n=169) PIH were recruited. We genotyped four polymorphisms in the GCM1 gene and examined the association with PIH using both logistic regression and likelihood expectation maximization (LEM) to adjust for intra-familial correlation between genotypes. Mat ...[more]

PMID: 21915358

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Project description:BACKGROUND:Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal programming may alter the fetal epigenome increasing the risk of metabolic disease in their offspring. The aims of this study were to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant methylation of CpG islands adjacent to targeted genes specific for obesity or diabetes disease pathways in a largely Hispanic population. METHODS:Methylation levels in the cord blood of 69 newborns were determined using the Illumina Infinium MethylationEPIC BeadChip. Over 850,000 different probe sites were analyzed to determine whether maternal obesity and/or diabetes mellitus directly attributed to differential methylation; epigenome-wide and regional analyses were performed for significant CpG sites. RESULTS:Following quality control, agranular leukocyte samples from 69 newborns (23 normal term (NT), 14 diabetes (DM), 23 obese (OB), 9 DM/OB) were analyzed for over 850,000 different probe sites. Contrasts between the NT, DM, OB, and DM/OB were considered. After correction for multiple testing, 15 CpGs showed differential methylation from the NT, associated with 10 differentially methylated genes between the diabetic and non-diabetic subgroups, CCDC110, KALRN, PAG1, GNRH1, SLC2A9, CSRP2BP, HIVEP1, RALGDS, DHX37, and SCNN1D. The effects of diabetes were partly mediated by the altered methylation of HOOK2, LCE3C, and TMEM63B. The effects of obesity were partly mediated by the differential methylation of LTF and DUSP22. CONCLUSIONS:The presented data highlights the associated altered methylation patterns potentially mediated by maternal diabetes and/or obesity. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the effects on newborn body composition and future health risk factors for metabolic disease. Additional future consideration should be targeted to the role of Hispanic inheritance. Potential future targeting of transgenerational propagation and developmental programming may reduce population obesity and diabetes risk.

Project description:Abstract Background Studies of inpatient coronavirus disease 2019 (COVID-19) mortality risk factors have mainly used data from academic medical centers or large multihospital databases and have not examined populations with large proportions of Hispanic/Latino patients. In a retrospective cohort study of 4881 consecutive adult COVID-19 hospitalizations at a single community hospital in Los Angeles County with a majority Hispanic/Latino population, we evaluated factors associated with mortality. Methods Data on demographic characteristics, comorbidities, laboratory and clinical results, and COVID-19 therapeutics were abstracted from the electronic medical record. Cox proportional hazards regression modeled statistically significant, independently associated predictors of hospital mortality. Results Age ≥65 years (hazard ratio [HR] = 2.66; 95% confidence interval [CI] = 1.90–3.72), male sex (HR = 1.31; 95% CI = 1.07–1.60), renal disease (HR = 1.52; 95% CI = 1.18–1.95), cardiovascular disease (HR = 1.45; 95% CI = 1.18–1.78), neurological disease (HR = 1.84; 95% CI = 1.41–2.39), D-dimer ≥500 ng/mL (HR = 2.07; 95% CI = 1.43–3.0), and pulse oxygen level <88% (HR = 1.39; 95% CI = 1.13–1.71) were independently associated with increased mortality. Patient household with (1) multiple COVID-19 cases and (2) Asian, Black, or Hispanic compared with White non-Hispanic race/ethnicity were associated with reduced mortality. In hypoxic COVID-19 inpatients, remdesivir, tocilizumab, and convalescent plasma were associated with reduced mortality, and corticosteroid use was associated with increased mortality. Conclusions We corroborate several previously identified mortality risk factors and find evidence that the combination of factors associated with mortality differ between populations. In our predominantly Hispanic/Latino community hospital adult population, we corroborate several previously identified COVID-19 mortality risk factors from academic medical center cohorts or large multihospital databases but conclude that the combination of factors differ from population to population.

Dataset Information

A fetal variant in the GCM1 gene is associated with pregnancy induced hypertension in a predominantly hispanic population.

Publications

A fetal variant in the GCM1 gene is associated with pregnancy induced hypertension in a predominantly hispanic population.

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