Association Study of GWAS-Derived Loci with Height in Brazilian Children: Importance of MAP3K3, MMP24 and IGF1R Polymorphisms for Height Variation

Autor(es)

Pereira Fontenele, Eveline Gadelha ^[1] ; Amaral de Moraes, Maria Elisabete ^[1] ; d'Alva, Catarina Brasil ^[1] ; Pinheiro, Daniel Pascoalino ^[1] ; Sales Pinheiro Landim, Sara Aguiar ^[2] ; de Sousa Barros, Fernando Antonio ^[3] ; Trarbach, Ericka Barbosa ^[4] ; de Mendonca, Berenice Bilharinho ^[5] ; Lima Jorge, Alexander Augusto ^[4]

Afiliação do(s) autor(es)

^[1] Univ Fed Ceara, Lab Farmacogenet, FARMAGEN, Unidade Farmacol Clin, Dept Fisiol & Farmacol, Fac, BR-60341970 Fortaleza, Ceara - Brazil

^[2] Univ Fortaleza, Fac Nutr, Fortaleza, Ceara - Brazil

^[3] Univ Fed Ceara, Hosp Univ Walter Cantidio, Unidade Endocrinol & Metab, BR-60341970 Fortaleza, Ceara - Brazil

^[4] Univ Sao Paulo, Fac Med, LIM 25, Unidade Endocrinol Genet, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med, Lab Hormonios & Genet Mol, LIM 42, Unidade Endocrinol Desenvolvimento, Discipl, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Hormone Research in Paediatrics; v. 84, n. 4, p. 248-253, 2015.
• Citações Web of Science: 2

Resumo

Background/Aim: The single nucleotide polymorphisms (SNPs) rs2282978 (CDK6), rs2425019 (MMP24), rs8081612 (MAP3K3), rs2871865 (IGF1R) and rs3782415 (SOCS2) were among the SNPs most strongly associated with height in a meta-analysis of 47 genome-wide association studies (GWAS) involving 114,223 adults from six ethnic groups. The present study aimed to examine associations between these SNPs and height in Brazilian children. Methods: Cross-sectional heights of 1,008 healthy unrelated 4.4- to 9.7-year-old children were evaluated. All genotypes were determined by allele-specific polymerase chain reactions. Height standard deviation scores (SDS) were generated for this population and regressed on allele counts. Linear regressions were performed to estimate the effect of individual SNPs or a polygenic allelic score on height. Results: The T allele of rs8081612 (MAP3K3), the C allele of rs2871865 (IGF1R) and the G allele of rs2425019 (MMP24) were significantly associated with a 0.091-SDS greater height (95% CI 0.089-0.093, p = 0.001) by polygenic analysis. The mean height SDS difference between children with 2 `tall' alleles and children with 4 `tall' alleles was 0.24 SDS (95% CI 0.05-0.43, p = 0.01). The observed allelic effect is consistent with that found in previous GWAS. Conclusions: Polymorphisms in MAP3K3, MMP24 and IGF1R act additively on height in children of an admixed population. These results demonstrate the importance of these loci for children's height. (C) 2015 S. Karger AG, Basel (AU)

• Processo FAPESP: 13/03236-5 - Novas abordagens e metodologias na investigação genético-molecular dos distúrbios de crescimento e desenvolvimento puberal
• Beneficiário: Alexander Augusto de Lima Jorge
• Modalidade de apoio: Auxílio à Pesquisa - Temático