A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness

Individual patients vary in their response to growth hormone (GH). No large-scale genome-wide studies have looked for genetic predictors of GH responsiveness. To identify genetic variants associated with GH responsiveness. Genome-wide association study (GWAS). Cohorts from multiple academic centers and a clinical trial. A total of 614 individuals from 5 short stature cohorts receiving GH: 297 with idiopathic short stature, 276 with isolated GH deficiency, and 65 born small for gestational age. Association of more than 2 million variants was tested. Primary analysis: individual single nucleotide polymorphism (SNP) association with first-year change in height standard deviation scores. Secondary analyses: SNP associations in clinical subgroups adjusted for clinical variables; association of polygenic score calculated from 697 genome-wide significant height SNPs with GH responsiveness. No common variant associations reached genome-wide significance in the primary analysis. The strongest suggestive signals were found near the B4GALT4 and TBCE genes. After meta-analysis including replication data, signals at several loci reached or retained genome-wide significance in secondary analyses, including variants near ST3GAL6. There was no significant association with variants previously reported to be associated with GH response nor with a polygenic predicted height score. We performed the largest GWAS of GH responsiveness to date. We identified 2 loci with a suggestive effect on GH responsiveness in our primary analysis and several genome-wide significant associations in secondary analyses that require further replication. Our results are consistent with a polygenic component to GH responsiveness, likely distinct from the genetic regulators of adult height

Maternal and perinatal outcomes after bariatric surgery: a spanish multicenter study

The final publication is avaliable at Springer Link[Abstract] Background. Bariatric surgery (BS) has become more frequent among women of child-bearing age. Data regarding the underlying maternal and perinatal risks are scarce. The objective of this nationwide study is to evaluate maternal and perinatal outcomes after BS. Methods. We performed a retrospective observational study of 168 pregnancies in 112 women who underwent BS in 10 tertiary hospitals in Spain over a 15-year period. Maternal and perinatal outcomes, including gestational diabetes mellitus (GDM), pregnancy-associated hypertensive disorders (PAHD), pre-term birth cesarean deliveries, small and large for gestational age births (SGA, LGA), still births, and neonatal deaths, were evaluated. Results were further compared according to the type of BS performed: restrictive techniques (vertical-banded gastroplasty, sleeve gastrectomy, and gastric banding), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion (BPD). Results. GDM occurred in five (3 %) pregnancies and there were no cases of PAHD. Women whose pregnancies occurred before 1 year after BS had a higher pre-gestational body mass index (BMI) than those who got pregnant 1 year after BS (34.6 ± 7.7 vs 30.4 ± 5.3 kg/m2, p = 0.007). In pregnancies occurring during the first year after BS, a higher rate of stillbirths was observed compared to pregnancies occurring after this period of time (35.5 vs 16.8 %, p = 0.03). Women who underwent BPD delivered a higher rate of SGA babies than women with RYGB or restrictive procedures (34.8, 12.7, and 8.3 %, respectively). Conclusions. Pregnancy should be scheduled at least 1 year after BS. Malabsorptive procedures are associated to a higher rate of SGA births

Association Between Advanced Maternal Age and Maternal and Neonatal Morbidity: A Cross-Sectional Study on a Spanish Population

Background and objective: Over recent decades, a progressive increase in the maternal age at childbirth has been observed in developed countries, posing a health risk for both women and infants. The aim of this study was to analyze the association between advanced maternal age (AMA) and maternal and neonatal morbidity. Material and methods: A cross-sectional study of 3,315 births was conducted in the north of Spain in 2014. We compared childbirth between women aged 35 years or older, with a reference group of women aged between 24 and 27 years. AMA was categorized based on ordinal ranking into 35-38 years, 39-42 years, and >42 years to estimate a dose-response pattern (the older the age, the greater the risk). As an association measure, crude and adjusted Odds Ratios (OR) were estimated by non-conditional logistic regression and 95% Confidence Intervals (95%CI) were calculated. Results: Repeated abortions were more common among women of AMA in comparison to pregnant women aged 24-27 years (reference group): adjusted OR = 2.68; 95%CI (1.52-4.73). A higher prevalence of gestational diabetes was also observed among women of AMA, reaching statistical significance when restricted to first time mothers: adjusted OR = 8.55; 95%CI (1.12-65.43). In addition, the possibility of an instrumental delivery was multiplied by 1.6 and the possibility of a cesarean by 1.5 among women of AMA, with these results reaching statistical significance, and observing a dose-response pattern. Lastly, there were associations between preeclampsia, preterm birth (<37 weeks) and low birthweight, however without reaching statistical significance. Conclusion: Our results support the association between AMA and suffering repeated abortions. Likewise, being of AMA was associated with a greater risk of suffering from gestational diabetes, especially among primiparous women, as well as being associated with both instrumental deliveries and cesareans among both primiparous and multiparous women

Serum alkaline phosphatase relates to cardiovascular risk markers in children with high calcium-phosphorus product

Although alkaline phosphatase (ALP) correlates with cardiovascular risk in adults, there are no studies in children. We evaluated the association between serum ALP levels, calcium-phosphorus product (Ca*P) and cardiovascular risk markers in healthy children. Children aged 7.9 ± 1.4 (n = 379) were recruited in this cross-sectional study. The main outcome measures were systolic and diastolic blood pressure (SBP and DBP) and carotid intima-media thickness (cIMT). Additional assessments were body-mass index (BMI), waist circumference, homeostatic model assessment of insulin resistance (HOMA-IR) and fasting lipids, ALP, serum calcium, phosphorus and Ca*P. ALP was directly correlated with BMI (p < 0.0001), waist circumference (p < 0.0001), SBP (p < 0.0001), cIMT (p = 0.005), HOMA-IR (p < 0.0001), and fasting triglycerides (p = 0.0001). Among them, in children with Ca*P values above the median the associations were BMI (r = 0.231; p = 0.001), waist (r = 0.252; p < 0.0001), SBP (r = 0.324; p < 0.0001), cIMT (r = 0.248; p = 0.001) and HOMA-IR (r = 0.291; p < 0.0001)]. ALP independently associated with SBP (β = 0.290, p < 0.001) and cIMT (β = 0.179, p = 0.013) in children with higher Ca*P, after adjusting for confounding variables. Circulating ALP is associated with a more adverse cardiovascular profile in children with higher Ca*P. We suggest that serum ALP and Ca*P levels could contribute to the assessment of risk for cardiovascular disease in children