Early Pubertal Maturation and Risk of Childhood Asthma: A Mendelian Randomization and Longitudinal Study

Abstract Introduction Observational studies suggest earlier puberty is associated with higher adulthood blood pressure (BP), but these findings have not been replicated using Mendelian randomization (MR). We examined this question sex-specifically using larger genome-wide association studies (GWAS) with more extensive measures of pubertal timing. Methods We obtained genetic instruments proxying pubertal maturation (age at menarche (AAM) or voice breaking (AVB)) from the largest published GWAS. We applied them to summary sex-specific genetic associations with systolic and diastolic BP z-scores, and self-reported hypertension in women (n=194174) and men (n=167020) from the UK Biobank, using inverse-variance weighting meta-analysis. We conducted sensitivity analyses using other MR methods, including multivariable MR adjusted for childhood obesity proxied by body mass index (BMI). We used late pubertal growth as a validation outcome. Results AAM (beta per one-year later = -0.030 [95% confidence interval (CI) -0.055, -0.005] and AVB (beta -0.058 [95% CI -0.100, -0.015]) were inversely associated with systolic BP independent of childhood BMI, as were diastolic BP (-0.035 [95% CI -0.060, -0.009] for AAM and -0.046 [95% CI -0.089, -0.004] for AVB) and self-reported hypertension (odds ratios 0.89 [95% CI 0.84, 0.95] for AAM and 0.87 [95% CI 0.79, 0.96] for AVB). AAM and AVB were positively associated with late pubertal growth, as expected. The results were robust to sensitivity analysis using other MR methods. Conclusion Timing of pubertal maturation was associated with adulthood BP independent of childhood BMI, highlighting the role of pubertal maturation timing in midlife BP.

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Towards a novel marker of insulin resistance in obesity: S100A4 in girls along the puberty. The longitudinal study “PUBMEP”

Proceedings of The Nutrition Society ◽

10.1017/s0029665120005959 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Augusto Anguita-Ruiz ◽

Andrea Méndez-Gutierrez ◽

Azahara I. Ruperez ◽

Rosaura Leis ◽

Gloria Bueno ◽

...

Keyword(s):

Insulin Resistance ◽

Longitudinal Study ◽

Molecular Mechanisms ◽

Pubertal Development ◽

Multiple Linear Regression Model ◽

Mixed Effects ◽

Adult Women ◽

Metabolic Risk ◽

Pubertal Maturation ◽

S100a4 Protein

AbstractIntroduction:Insulin resistance (IR) is the major driver for the development of obesity-associated metabolic and cardiovascular complications. It is well known that IR increase physiologically during puberty; hence, pubertal maturation might favour this metabolic risk in obese children. Recently, a study carried out in adult women with obesity has identified a new adipokine, known as S100A4, strongly associated with IR and inflammation in adipose tissue. On the contrary, little is known about the implication of S100A4 in the development of such metabolic disturbances during the onset and course of pubertal development.Materials and methods:A longitudinal study was conducted on 53 Spanish girls distributed in six experimental conditions according to their obesity and IR status (before (T0) and after (T1) the onset of puberty). Anthropometric and biochemical parameters were evaluated in all samples and time points. Classification of pubertal stage was made according to the Tanner scale. S100A4 protein levels were quantified by ELISA CSB-EL02032HU in plasma samples (Cusabio Biotech, Wuhan, China). The statistical analysis of the results was carried out with the “nlme” package in R v3.4.4, using a mixed-effects linear model with random intercept and slope.Results:At a significance level of alpha = 0.05, a linear mixed-effects model reported a significant association (P = 0.03) between the interaction term “time*experimental group” and S100A4 levels. Post-hoc pairwise comparisons between experimental groups revealed a strong association between a worsening/improvement of the IR status and the increase/decrease of S100A4 levels (yielding significant results for 5 of the 15 comparisons (P = 0.008, P = 0.04, P = 0.02, P = 0.04 and P = 0.02)). Furthermore, a multiple linear regression model reported a positive correlation between the increase in S100A4 levels and the increase in HOMA values during the course of puberty (B = 6.03, SE = 2.66 and P = 0.028).Discussion:The S100A4 protein is strongly associated with the development of IR in girls with childhood obesity and this association is accentuated during pubertal development. Increase in S100A4 levels could be one of the molecular mechanisms by which pubertal maturation favour an increased metabolic risk in children with obesity.

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