The online version of this article (https://doi.org/10.1186/s12902-018-0271-1) contains supplementary material, which is available to authorized users.
Insulin and insulin-like growth factor (IGF)-1 coupled with growth hormone helps control timing of sexual maturation. Mutations and variants in multiple genes are associated with development or reduced risk of central precocious puberty (CPP).
We assessed single nucleotide polymorphisms (SNPs) in the IGF-1, IGF-2, IGF-3, IGF-1 receptor (IGF1R), IGF-2 receptor (IGF2R), and IGF -binding protein 3 (IGFBP-3) genes, and their association with demographics and metabolic proteins in girls with CPP. Z-scores of height, weight, and body mass index (BMI) were calculated with the WHO reference growth standards for children.
IGF-1 serum levels of CPP group exhibited a higher correlation with bone age, z-scores of height and weight, and luteinizing hormone (LH) than those of control group, regardless of BMI adjustment. In the CPP group, height was associated with IGF-2(3580), an adenine to guanine (A/G) SNP at position + 3580. BMI in the CPP group was associated with IGF-2(3580), IGF1R, and the combinations of [IGF-2(3580) + IGF2R], and [IGF-2(3580) + IGFBP-3]. Body weight in the CPP group was associated with the combination of [IGF-2(3580) + IGFBP-3] (p = 0.024). Weight and BMI were significantly associated with the combination of [IGF-2(3580) + IGF2R + IGFBP-3] in the CPP group. These associations were not significantly associated with z-scores of weight, height, or BMI. The distribution of these genotypes, haplotypes, and allele frequencies were similar between control and CPP groups.
These known SNPs of these IGF-1 axis genes appear to play minor roles in the risk for development of CPP.
Additional file 1: Table S1. Distribution of SNPs in IGF1R, IGF-1(6093), IGF-1(1770), IGF-2(3123), IGF2R, IGF-2(3580), IGFBP-3, and insulin in CPP and control groups. Table S2–1 Summary of genotype distribution of two SNP combinations in two distinct genes by group. Table S2–2. (continued) Summary of genotype distribution in two SNP combinations in two distinct genes by group. Table S3–1. Associations between demographic and pathological features and SNP genotypes in control group. Table S3–2. Associations between demographic and pathological features and SNP genotypes in CPP group. Table S4–1. Comparison of associations between demographic and pathological features with two SNP genotype combinations in the control group. Table S4–2. Associations between demographic and pathological features and two SNP genotype combinations in the CPP group. Table S5–1. Associations between demographic and pathological features and combinations of IGFBP-3 and two additional genes in the control group. Table S5–2. Associations between demographic and pathological features and combinations of IGFBP-3 and two additional genes in the CPP group. Table S6. Summary of the power for given control and CPP groups. (DOCX 144 kb)12902_2018_271_MOESM1_ESM.docx
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