Polymorphism in the insulin-like growth factor 1 gene is associated with age at menarche in caucasian females

The Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.
Human Reproduction (Impact Factor: 4.57). 07/2007; 22(6):1789-94. DOI: 10.1093/humrep/dem052
Source: PubMed


The insulin-like growth factor 1 (IGF1) gene, which plays a crucial role in hypothalamic-pituitary-ovarian hormone-controlled metabolic processes, may influence the onset of menarche. Our study aimed to test association between IGF1 polymorphisms with the variation of age at menarche (AAM) in Caucasian females.
We recruited a sample of 1048 females from 354 Caucasian nuclear families and genotyped 19 single-nucleotide polymorphisms (SNPs) spanning the entire IGF1 gene. Pairwise linkage disequilibrium among SNPs was measured, and the haplotype blocks were inferred. Both single SNP markers and haplotypes were tested for association with AAM using the quantitative transmission disequilibrium test.
Significant association (P = 0.0153) between AAM and SNP3 (rs6214) in block1 was detected.
Our results suggested a potential effect of SNP3 in the IGF1 gene on AAM variation in Caucasian women for the first time. However, further independent studies are needed to confirm our findings.

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Available from: Yan Guo, Nov 26, 2014
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    • "Several single-nucleotide polymorphisms in IGF-1 are reported to play an important role in the risk of cancer, myopia, muscle function, and BMD regulation (Kostek et al., 2010). A previous study showed that rs35767, rs2288377, and rs5742612 of IGF-1 can influence the expression of IGF-1 (Zhao et al., 2007); however, few studies have investigated the association between single nucleotide polymorphisms in IGF-1 and the risk of osteoporosis in Chinese female populations. Therefore, we examined the relationship between rs35767, rs2288377, and rs5742612 in IGF-1 and the risk of osteoporosis in a Chinese female population. "
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    ABSTRACT: We conducted a case-control study to assess the relationship between rs35767, rs2288377, and rs5742612 insulin-like growth factor-1 (IGF-1) and osteoporosis risk in a Chinese female population. The genotypes of rs35767, rs2288377, and rs5742612 of IGF-1 were determined by polymerase chain reaction-restriction fragment length polymorphism. Patients with osteoporosis were more likely to have drinking and smoking habits and have lower bone mineral density in the L2-L4 vertebrae, femoral neck, and total hip. According to conditional regression analysis, individuals carrying the TT genotype of rs35767 had an increased risk of osteoporosis, with an adjusted odds ratio (95% confidence interval) of 2.29 (1.35-4.97). In conclusion, our results suggest that the TT genotype of IGF-I rs35767 was associated with an increased risk of osteoporosis, suggesting that this polymorphism can be used as a predictive factor for osteoporosis risk.
    Preview · Article · Jul 2015 · Genetics and molecular research: GMR
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    • "However, previous studies also suggested no relationship between IGF-1 and BMD,14 and reported that the low levels of circulating IGF-1 had no actually relation with osteoporosis.15 Several SNPs of IGF-1 have been recognized to be involved in cancer, myopia, muscle function, BMD regulation and affects age at menarche.16,17 However, study investigated the links between polymorphisms of IGF-I and BMD or osteoporosis is lacking. "
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    ABSTRACT: Objective: It has been shown that Insulin-like growth factor-1 (IGF-1) may be related with bone mineral density (BMD) or osteoporosis. But there are few evidences on the role of genetic variation of IGF-1 on the BMD or osteoporosis. We observed the relationship between polymorphisms of IGF-1(rs35767, rs2288377 and rs5742612) with osteoporosis and BMD in the postmenopausal female population in our study. Methods: A total of 216 postmenopausal women with a primary diagnosis of osteoporosis and 220 normal healthy women were included in the study. Genomic DNA of IGF-1 rs35767, rs2288377 and rs5742612 was extracted from the whole blood using QIAamp blood DNA mini kits (QIAGEN, Hilden, Germany) according to the methods recommended by the manufacturer. Results: We found that T allele of rs35767 had higher increased risk of osteoporosis (OR=1.34, 95%CI=1.0-1.81). Those carrying T allele of rs35767 had a significant lower BMD at L1–L4 vertebrae, femoral neck, total hip and trochanter when compared with those carrying C allele (P < 0.05). In addition, the BMD of L1–L4 vertebrae, femoral neck, total hip and trochanter decreased by 2.09%, 3.74%, 3.52% and 2.54% in women carrying T alleles compared with those carrying C alleles. Conclusion: Our study suggests that polymorphism in IGF-I rs35767 was significantly associated with BMD and osteoporosis in postmenopausal female population, and polymorphism of rs35767 could be a marker for lower BMD and risk of osteoporosis.
    Full-text · Article · Mar 2014 · Pakistan Journal of Medical Sciences Online
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    • "Higher serum levels of IGF1 and a single nucleotide polymorphisms (SNP) in IGF1R were associated with premature pubarche in humans (Roldan et al. 2007). Furthermore, the IGF1 gene is located in a quantitative trait locus found for age at menarche (Anderson et al. 2008), and a SNP in exon 4 of IGF1 was associated with age at menarche in women (Zhao et al. 2007). In Brahman cattle, serum concentration of IGF1 was found to be negatively correlated (r = À0.7 at 18 months of age, r = À0.43 at 24 months of age) with age of puberty (Johnston et al. 2009). "
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    ABSTRACT: Insulin-like growth factor I (somatomedin C) (IGF1) influences gonadotrophin-releasing hormone (GnRH) neurons during puberty, and GnRH release guides pubertal development. Therefore, genes of the IGF1 pathway are biological candidates for the identification of single-nucleotide polymorphisms (SNPs) affecting age of puberty. In a genome-wide association study, genotyped heifers were Tropical Composite (TCOMP, n = 866) or Brahman (BRAH, n = 843), with observation of age at first corpus luteum defining puberty. We examined SNPs in or near genes of the IGF1 pathway and report seven genes associated with age at puberty in cattle: IGF1R, IGFBP2, IGFBP4, PERK (HUGO symbol EIF2AK3), PIK3R1, GSK3B and IRS1. SNPs in the IGF1 receptor (IGF1R) showed the most promising associations: two SNPs were associated with puberty in TCOMP (P < 0.05) and one in BRAH (P = 0.00009). This last SNP explained 2% of the genetic variation (R(2) = 2.04%) for age of puberty in BRAH. Hence, IGF1R was examined further. Additional SNPs were genotyped, and haplotypes were analysed. To test more SNPs in this gene, four new SNPs from dbSNP were selected and genotyped. Single SNP and haploytpe analysis revealed associations with age of puberty in both breeds. There were two haplotypes of 12 IGF1R SNPs associated with puberty in BRAH (P < 0.05) and one in TCOMP (P < 0.05). One haplotype of two SNPs was associated (P < 0.01) with puberty in BRAH, but not in TCOMP. In conclusion, the IGF1 pathway appeared more relevant for age of puberty in Brahman cattle, and IGF1R showed higher significance when compared with other genes from the pathway.
    Full-text · Article · May 2012 · Animal Genetics
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