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Associations between menarche-related genetic variants and pubertal growth in male and female adolescents.

ABSTRACT: PURPOSE:Previous studies have identified novel genetic variants associated with age at menarche in females of European descent. The pubertal growth effects of these variants have not been carefully evaluated in non-European descent groups. We aimed to examine the effects of 31 newly identified menarche-related single-nucleotide polymorphisms (SNPs) on growth outcomes in African-American (AA) and European-American (EA) children in a prospective cohort. METHODS:We analyzed longitudinal data collected from 263 AAs and 338 EAs enrolled between ages 5 and 17 years; the subjects were followed semiannually for an average of 6 years. The associations between the SNPs and growth-related outcomes, including weight, height, and body mass index (BMI), were examined using mixed-effect models. RESULTS:Longitudinal analyses revealed that 4 (near or in genes VGLL3, PEX2, CA10, and SKOR2) of the 14 menarche-only-related SNPs were associated with changes in weight and BMI in EA and AA (p ? .0032), but none of them was associated with changes in height. Of the eight menarche-timing and BMI-related SNPs, none was associated with changes in height, but three (in or near genes NEGR1, ETV5, and FTO) were associated with more rapid increases in weight and/or BMI in EA (p ? .0059). Among the nine menarche-timing and height-related SNPs, four (in or near genes ZBTB38, LOC728666, TBX2, and CABLES) were associated with changes in weight or height in EA and AA (p ? .0042). CONCLUSIONS:Genetic variants related to age at menarche were found to be associated with various growth parameters in healthy adolescents. The identified associations were often race and sex specific.

SUBMITTER: Tu W

PROVIDER: S-EPMC4275397 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Associations between menarche-related genetic variants and pubertal growth in male and female adolescents.

Tu Wanzhu W Wagner Erin K EK Eckert George J GJ Yu Zhangsheng Z Hannon Tamara T Pratt J Howard JH He Chunyan C

The Journal of adolescent health : official publication of the Society for Adolescent Medicine 20141003 1

<h4>Purpose</h4>Previous studies have identified novel genetic variants associated with age at menarche in females of European descent. The pubertal growth effects of these variants have not been carefully evaluated in non-European descent groups. We aimed to examine the effects of 31 newly identified menarche-related single-nucleotide polymorphisms (SNPs) on growth outcomes in African-American (AA) and European-American (EA) children in a prospective cohort.<h4>Methods</h4>We analyzed longitudi ...[more]

PMID: 25287989

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Project description:BACKGROUND:Meta-analysis of genome-wide association studies identified obesity-related genetic variants. Due to the pleiotropic effects of related phenotypes, we tested six of these obesity-related genetic variants for their association with physical activity: fat mass and obesity-associated (FTO)(rs9939609)T>A, potassium channel tetramerization domain containing (KCTD15) (rs11084753)G>A, melanocortin receptor4 (MC4R)(rs17782313)T>C, neuronal growth regulator 1 (NEGR1)(rs2815752)A>G, SH2B adapter protein 1 (SH2B1)(rs7498665)A>G, and transmembrane protein18 (TMEM18)(rs6548238)C>T. METHOD:European-American women (n = 263) and men (n = 229) (23.5 ± 0.3 years, 24.6 ± 0.2 kg/m2) were genotyped and completed the Paffenbarger physical activity Questionnaire. Physical activity volume in metabolic energy equivalents [MET]-hour/week was derived from the summed time spent (hour/week) times the given MET value for vigorous, moderate, and light intensity physical activity, and sitting and sleeping, respectively. Multivariable adjusted [(age, sex, and body mass index (BMI)] linear regression tested associations among genotype (dominant/recessive model) and the log of physical activity volume. RESULT:MC4R (rs17782313)T>C explained 1.1 % (p = 0.02), TMEM18(rs6548238)C>T 1.2 % (p = 0.01), and SH2B1 (rs7498665)A>G 0.6 % (p = 0.08) of the variability in physical activity volume. Subjects with the MC4R C allele spent 3.5 % less MET-hour/week than those with the TT genotype (p = 0.02). Subjects with the TMEM18 T allele spent 4.1 % less MET-hour/week than those with the CC genotype (p = 0.01). Finally, subjects with the SH2B1 GG genotype spent 3.6 % less MET-hour/week than A allele carriers (p = 0.08). CONCLUSION:Our findings suggest a shared genetic influence among some obesity-related gene loci and physical activity phenotypes that should be explored further. Physical activity volume differences by genotype have public health importance equating to 11-13 lb weight difference annually.

Project description:BackgroundThe majority children living with HIV infection now survive into adulthood because of effective antiretroviral therapy (ART), but few data exist on their growth during adolescent years. This study investigated growth patterns and evaluated factors associated with suboptimal growth in adolescents with perinatally-acquired HIV infection.MethodsThis retrospective cohort study included HIV-infected adolescents, aged 13 to 18 years, with at least 5 years of ART follow-up at a large HIV clinic in the Gauteng Province, South Africa. Weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ) and body mass index (BMI)-for-age Z-scores were calculated using World Health Organization (WHO) growth standards. Growth velocity graphs were generated utilising the mean height change calculated at 6-monthly intervals, using all available data after ART initiation, to calculate the annual change. Other collected data included WHO HIV disease staging, CD4%, HIV viral loads (VLs), ART regimens and tuberculosis co-infection.ResultsIncluded were 288 children with a median age of 6.5 years (IQR 4.2;8.6 years) at ART initiation, and 51.7% were male. At baseline the majority of children had severe disease (92% WHO stages 3&4) and were started on non-nucleoside reverse transcriptase inhibitor-based regimens (79.2%). The median CD4% was 13.5% (IQR 7.9;18.9) and median HIV viral load log 5.0 (IQR 4.4;5.5). Baseline stunting (HAZ <-2) was prevalent (55.9%), with a median HAZ of -2.2 (IQR -3.1;-1.3). The median WAZ was -1.5 (IQR -2.5;-0.8), with 29.2% being underweight-for-age (WAZ <-2). The peak height velocity (PHV) in adolescents with baseline stage 3 disease was higher than for those with stage 4 disease. Being older at ART start (p<0.001) and baseline stunting (p<0.001) were associated with poorer growth, resulting in a lower HAZ at study exit, with boys more significantly affected than girls (p<0.001).ConclusionsSuboptimal growth in adolescents with perinatally-acquired HIV infection is a significant health concern, especially in children who started ART later in terms of age and who had baseline stunting and is more pronounced in boys than in girls.

Dataset Information

Associations between menarche-related genetic variants and pubertal growth in male and female adolescents.

Publications

Associations between menarche-related genetic variants and pubertal growth in male and female adolescents.

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