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Objective:Common genetic variants in the gene encoding uromodulin (UMOD) have been associated with renal function, blood pressure (BP) and hypertension. We investigated the associations between an important single nucleotide polymorphism (SNP) in UMOD, that is rs12917707-G>T, and estimated glomerular filtration rate (eGFR), BP and cardiac organ damage as determined by echocardiography in patients with arterial hypertension.Methods:A cohort of 1218 treated high-risk patients (mean age 58.5 years, 83% men) with documented cardiovascular disease (81% with coronary heart disease) was analysed.Results:The mean values for 24-h SBP and DBP were 124.714.7 and 73.9 +/- 9.4mmHg; mean eGFR was 77.5 +/- 18.3ml/min per 1.73m(2), mean left ventricular ejection fraction was 59.3 +/- 9.9% and mean left ventricular mass index in men and women was 53.9 +/- 23.2 and 54.9 +/- 23.7g/m(2.7) with 50.4% of patients having left ventricular hypertrophy. A significant association between rs12917707 and eGFR was observed with T-allele carriers showing significantly higher eGFR values (+2.6ml/min per 1.73m(2), P=0.006) than noncarriers. This SNP associated also with left atrial diameter (P=0.007); homozygous carriers of the T-allele had smaller left atrial diameter (-1.5mm) than other genotype groups (P=0.040). No significant associations between rs12917707 and other cardiac or BP phenotypes were observed.Conclusions:These findings extend the previously documented role of UMOD for renal function also to treated high-risk patients with arterial hypertension and reveal a novel association with left atrial remodelling and thus a potential cardiorenal link modulated by UMOD.
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 Â 10 À8 . In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.