Genetic variation of FTO and TCF7L2 in premature adrenarche

Lappalainen, Saila; Voutilainen, Raimo; Utriainen, Pauliina; Laakso, Markku; Jääskeläinen, Jarmo

doi:10.1016/j.metabol.2009.03.025

Cited by 9 publications

(9 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many efforts have been made to identify factors that stimulate adrenarche; ACTH, IGF-1, insulin, cortisol, adrenal medulla, and obesity have been proposed to play roles [1,8,9,23]. The higher IGF-1 levels and advanced BA in PP compared to NC girls observed in the current study, confirming previous findings [23,24], might be interpreted as the underlying mechanisms of the early growth pattern exhibited by PP subjects.…”

Section: Discussionsupporting

confidence: 87%

“…As with all steroid hormones, the binding of androgens to the androgen receptor (AR) triggers a conformational change in the AR-androgen complex, which is then transported into the nucleus where it binds to DNA [7]. Numerous endogenous or exogenous signals that stimulate the secretion of adrenal androgen secretions have been proposed [1,8,9] but not all PP children exhibit increased androgen levels [10]. Therefore, the response of the pilosebaceous unit to androgens may also influence the development of the condition.…”

Section: Subjectsmentioning

confidence: 99%

See 1 more Smart Citation

Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls

Kang¹,

Lee

Kim

et al. 2017

Endocr J

View full text Add to dashboard Cite

Abstract. The CAG repeat length of the androgen receptor (AR) gene, which exhibits an inverse relationship to AR sensitivity, might influence the development of the pubarche along with hyperandrogenemia. There are ethnic differences in the AR CAG repeat length, however, no Asian studies on premature pubarche (PP) have been reported, including Korea. Our objectives were to examine the hormone levels and AR CAG repeat length, and to assess their contributions to PP in Korean girls. Subjects with PP (n=16) and normal pubarche (NP, n=16), and normal controls (NC, n=16) were enrolled. The levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and free testosterone (FT) were checked. The methylation-weighted (MW) average CAG repeat lengths were analyzed. The median ages at pubarche were 7.4 and 8.9 years in the PP and NP groups, respectively, and the levels of 17-OHP, DHEAS, and FT were similar in both groups. The PP group exhibited a higher DHEAS:DHEA ratio than the NP group (P=0.014). The medians of the MW average CAG repeat length of the AR gene were 22.4 for all subjects and did not differ among the PP (22.3), NP (22.4), and NC (22.2) groups. The AR CAG repeat lengths in the PP and NP groups did not correlate with DHEAS or FT levels. These results suggest that the AR CAG repeat length was not involved in the development of PP in Korean girls. However, excessive adrenal androgen levels, particularly those caused by increased sulfotransferase activity, might be important in the pathogenesis of PP.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Subjectsmentioning

confidence: 99%

Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls

Kang¹,

Lee

Kim

et al. 2017

Endocr J

View full text Add to dashboard Cite

show abstract

“…In addition, an ACTH receptor polymorphism has been found to be associated with the severity of PA also indicating a modulatory effect of the hypothalamic-pituitary-adrenal (HPA) axis in this condition (37). In the same cohort, Lappalainen et al (38) could also show that mean CAG repeat length of the androgen receptor (AR) gene is shorter in PA girls and that a polymorphic allele of the transcription factor TCF7L2, involved in the Wnt signalling pathway, was more frequent in PA subjects (39). However, genomewide association studies in appropriately powered cohorts of children with early androgen excess are currently lacking.…”

Section: Adrenarche Pubarche and Pubertymentioning

confidence: 94%

Premature adrenarche: novel lessons from early onset androgen excess

Idkowiak

Lavery

Dhir

et al. 2011

European Journal of Endocrinology

110

View full text Add to dashboard Cite

Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

show abstract

“…Several studies have searched for genetic factors predisposing to premature juvenility in genes involved in steroid synthesis [33,34], androgen action [35,36], IGF functions [37,38], and the Wnt signaling TCF7L2 [39]. Although some associations have been found, the underlying susceptibility genes remain largely unknown.…”

Section: Premature Juvenilitymentioning

confidence: 99%

Evo-Devo of Child Growth III: Premature Juvenility as an Evolutionary Trade-Off

Hochberg

2010

Horm Res Paediatr

View full text Add to dashboard Cite

Juvenility was previously defined as a distinct clinical life history stage, characterized by adrenarche, decelerating growth and accelerating adiposity. This review presents the theory of evolutionary predictive adaptive strategies for premature juvenility in response to (mostly) energy supply, but also to other environmental cues. In the absence of longitudinal adrenal androgen levels, premature juvenility can be diagnosed by auxological criteria. Syndromes of short stature that are associated with premature juvenility include Prader-Willi syndrome, Silver-Russell syndrome and Noonan syndrome, and it is part of the pygmy adaptive shortness of stature. The review elucidates in evolutionary terms the association of premature juvenility with SGA and PCOS.

show abstract

Genetic variation of FTO and TCF7L2 in premature adrenarche

Cited by 9 publications

References 54 publications

Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls

Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls

Premature adrenarche: novel lessons from early onset androgen excess

Evo-Devo of Child Growth III: Premature Juvenility as an Evolutionary Trade-Off

Contact Info

Product

Resources

About