IGF-1 gene therapy prevents spatial memory deficits and modulates dopaminergic neurodegeneration and inflammation in a parkinsonism model.

Cognitive impairment in Parkinson's disease is considered an indicator of the prodromal stages of this condition, occurring prior to the onset of classic and pathognomonic motor symptoms. Among other factors, neuroinflammation is increasingly recognized as a potential mediator of this neurodegenerative process, and glial cells are directly involved. However, the use of neurotrophic factors is associated with neuroprotection and cognitive improvements. Among all those factors, insulin-like growth factor 1 (IGF-1) has attracted considerable attention. In this study, we aimed to investigate the effect of IGF-1 gene therapy in an early animal model of 6-hydroxidopamine (6-OHDA)- induced parkinsonism. For this purpose, we employed male Wistar rats. The animals were first divided into two groups according to the bilateral injection into de Caudate Putamen unit (CPu):(a) VEH group (vehicle solution) and (b) 6-OHDA group (neurotoxic solution). After that, the animals in each group were divided, according to the bilateral injection into the dorsal hippocampus, in a control group (who received a control virus RAd-DSRed) and an experimental group (who received a therapeutic virus (RAd-IGF1). After three weeks of exposure to 6-OHDA, our study showed that IGF-1 gene therapy improved cognitive deficits related to short-term and spatial working memory, it also increased expression levels of tyrosine hydroxylase in the CPu. In addition, the therapy resulted in significant changes in several parameters (area, perimeter, roundness, ramification, and skeleton ́s analyses) related to microglia and astrocyte phenotypes, particularly in the CPu and dorsal hippocampal areas. Our data support the use of IGF-1 as a therapeutic molecule for future gene transfer interventions, that will contribute to a better understanding of the mechanisms correlating cognitive function and inflammatory process.

Influence of single nucleotide polymorphism in the IGF-1 gene on performance and conformation traits in Munjal sheep.

Genetic polymorphism research in livestock species aims to assess genetic differences within and among breeds, primarily for conservation and development objectives. The aim of the present study was to determine the point mutation in the IGF-1 gene (g.855G>C and g.857G>A) and its association with performance traits in Munjal sheep. In total, 50 Munjal sheep were selected and the genomic DNA was isolated using the Automated Maxell RSC DNA/RNA purification system and the Maxwell RSC whole blood DNA kit. A reported set of primers was used to amplify the 294-bp fragment encompassing the targeted region, i.e. the 5' flanking region of the IGF-1 gene. The polymerase chain reaction product of 294-bp size harbouring the g.857G>A mutation in the 5' flanking region of the IGF-1 gene was digested with HaeII enzyme. Three possible genotypes were defined by distinct banding patterns, i.e. GG (194, 100 bp), GA (294, 194, 100 bp) and AA (294 bp) in the studied population of Munjal sheep. The genotypic and allelic frequencies of g.857G>A single nucleotide polymorphism of the IGF-1 gene indicated that the frequency of the A allele was higher in the studied population, i.e. 0.59 and the GA genotype was found to be the predominant genotype (0.66). Allele A of the IGF-1 gene was found to be associated with higher body weights and can be used in selection criteria for improving the performance of Munjal sheep. The positive effect of the IGF-1 gene on several conformational traits as observed in this study suggests that this area of the ovine IGF-I gene is particularly important and warrants further investigation on a larger population size.

Transient B-cell depletion and regulatory T-cells mediation in combination with adenovirus mediated IGF-1 prevents and reverses autoimmune diabetes in NOD mice.

Type 1 diabetes (T1D) is one of the T cells mediated autoimmune diseases, although B cells also play an important role in the development. Both T cell and B cell targeted immunotherapies exhibited efficacies in preventing and reversing the T1D. Current study was performed to investigate the protective effects of anti-CD20/CD3 bi-specific antibody (bsAb) in combination with adenovirus mediated mouse insulin-like growth factor 1 (Adv-mIGF-1) gene on T1D in non-obese diabetes (NOD) mice. To simultaneously restore the proportion of Th cells and block the interaction of B cells as well as mediate T cell populations, the NOD model mice were randomly assigned to four groups received the saline, anti-CD20/CD3 bsAb and Adv-mIGF-1 gene alone or combination, respectively. After 16-consecutive weeks intervention, the ELISA, RT-PCR, western blot and histopathological analysis were performed to assess the pancreatic tissues and serum samples to evaluate the treatment effects. Chronic treatment of combination therapy improved T1D morbidity by improving the compartment and function of the CD4+Foxp3+ Tregs, reversing the secretion of insulin, controlling the blood glucose levels (BGLs) and alleviating insulitis as well as cell apoptosis in the NOD model mice. Moreover, current combination therapy also accelerated the proliferation and differentiation of pancreatic ß cells via suppressing the apoptosis-related factors, including caspase-3, caspase-8 and Fas, and activating the Bcl-2-related anti-apoptotic pathway. Furthermore, the cytokeratin-19 (CK-19) and pancreatic duodenal homoplasmic box-1 (PDX-1), as two important stem cell markers of pancreas were both significantly improved by treatment of combination therapy. On conclusions, chronic treatment of anti-CD20/CD3 bsAb in combination with Adv-mIGF-1 gene exerts synergistic protection on T1D in the NOD mice.

Effect of intra-BLA overexpression of IGF-1 on the expression of a contextual fear memory trace.

Growth factors, such as insulin-like growth factor 1 (IGF-1), among others are known for their critical involvement in learning and memory processes. IGF-1 regulates cognitive functions, synapse density, neurotransmission, and adult neurogenesis and induces structural and synaptic plasticity-specific changes. Although IGF-1 has been suggested to participate in different memory processes, its role in memories associated with negative emotional experiences still remains to be elucidated. The principal aim of the present study was to test whether IGF-1 overexpression using adenoviral vectors in basolateral amygdala (BLA) influences both the expression and formation of contextual fear memory, as well as the hippocampal structural plasticity associated with such memory trace. We found that IGF-1 overexpression promotes the formation and expression of a specific contextual fear memory trace, and such effect persisted at least 7 days after recall. Moreover, the overexpression of this growth factor in BLA upregulates the activation of the ERK/MAPK pathway in this brain structure. In addition, intra-BLA IGF-1 overexpression causes dorsal hippocampus (DH) structural plasticity modifications promoting changes in the proportion of mature dendritic spines in the CA1 region, after a weak conditioning protocol. The present findings contribute to the knowledge underlying BLA-DH trace memory of fear and reveal important new insights into the neurobiology and neurochemistry of fear acquisition modulated by IGF-1 overexpression. The understanding of how IGF-1 modulates the formation of a fear contextual trace may pave the way for the development of novel therapeutic strategies focused on fear, anxiety, and trauma-related disorders.

Association of rs5742612 Polymorphism in the Promoter Region of IGF1 Gene with Nonalcoholic Fatty Liver Disease: A Case-Control Study.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is an emerging global chronic liver disease encompassing a wide spectrum of disorders ranging from simple steatosis to nonalcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Considering the strong association between NAFLD and insulin resistance, and the vital role of insulin-like growth factor 1 (IGF1) in IR, we hypothesized that IGF1 gene polymorphism might be associated with NAFLD. METHODS: A total of 302 subjects, including 149 patients with biopsy-proven NAFLD and 153 controls, were enrolled in this case-control study. All the subjects were genotyped for the rs5742612 polymorphism of the IGF1 gene using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The distribution of IGF1 rs5742612 genotypes and alleles differed significantly between the cases with NAFLD and controls. The IGF1 rs5742612 CC genotype compared with the TT genotype or the TT+TC genotype occurred more frequently in the cases than the controls and the differences remained significant after adjustment for confounding factors such as age and body mass index (P = .011, OR = 2.71, 95%CI = 1.16-5.85; and P = .032, OR = 2.29, 95% CI = 1.10-5.24, respectively). CONCLUSION: For the first time, this study uncovered that the IGF1 rs5742612 CC genotype compared with the TT genotype or the TT+TC genotype had a 2.71-fold or 2.29-fold increased risk for NAFLD, respectively.

IGF-1 Gene Transfer Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain.

Brain aging is characterized by chronic neuroinflammation caused by activation of glial cells, mainly microglia, leading to alterations in homeostasis of the central nervous system. Microglial cells are constantly surveying their environment to detect and respond to diverse signals. During aging, microglia undergoes a process of senescence, characterized by loss of ramifications, spheroid formation, and fragmented processes, among other abnormalities. Therefore, the study of changes in microglia during is of great relevance to understand age-related declines in cognitive and motor function. We have targeted the deleterious effects of aging by implementing IGF-1 gene transfer, employing recombinant adenoviral vectors (RAds) as a delivery system. In this study, we performed intracerebroventricular (ICV) RAd-IGF-1 or control injection on aged female rats and evaluated its effect on caudate-putamen unit (CPu) gene expression and inflammatory state. Our results demonstrate that IGF-1 overexpression modified aged microglia of the CPu towards an anti-inflammatory condition increasing the proportion of double immuno-positive Iba1+Arg1+ cells. We also observed that phosphorylation of Akt was increased in animals treated with RAd-IGF-1. Moreover, IGF-1 gene transfer was able to regulate CPu pro-inflammatory environment in female aged rats by down-regulating the expression of genes typically overexpressed during aging. RNA-Seq data analysis identified 97 down-modulated DEG in the IGF-1 group as compared to the DsRed one. Interestingly, 12 of these DEG are commonly overexpressed during aging, and 9 out of 12 are expressed in microglia/macrophages and are involved in different processes that lead to neuroinflammation and/or neuronal loss. Finally, we observed that IGF-1 overexpression led to an improvement in motor functions. Although further studies are necessary, with the present results, we conclude that IGF-1 gene transfer is modifying both the pro-inflammatory environment and activation of microglia/macrophages in CPu. In this regard, IGF-1 gene transfer could counteract the neuroinflammatory effects associated with aging and improve motor functions in senile animals.

The relationship between polymorphism of insulin-like growth factor I gene and susceptibility to type 2 diabetes in Uygur population, Xinjiang, China.

BACKGROUND: Type 2 diabetes (T2DM) susceptibility varies among different populations and is affected by gene single nucleotide polymorphism (SNP). Insulin-like growth factor (IGF)-1 gene, which has many SNP loci, is involved in T2DM pathogenesis. However, the relationship of IGF-1 gene polymorphism with T2DM in Uyghur population is less studied. OBJECTIVE: To investigate the relationship between T2DM susceptibility and polymorphism of IGF-1 gene in Uyghur population of Xinjiang, China. METHODS: This study enrolled 220 cases (122 males (55.46%) and 98 females (44.54%); mean age of 53.40 ± 10.94 years) of T2DM patients (T2DM group) and 229 (124 males (54.15%) and 105 females (45.85%); mean age of 51.64 ± 10.48 years) healthy controls (control group). Biochemical indexes were determined. IGF-1 gene polymorphism was analyzed by SNP genotyping. RESULTS: The levels of TG, HDL, LDL, BUN, and Cr were statistically significant between the T2DM group and the control group. In terms of IGF-1 polymorphism, T2DM group had higher frequency of AA genotype (OR = 2.40, 95% CI = 1.19-4.84) and allele A (OR = 1.55, 95% CI = 1.17-2.06) of rs35767 loci, suggesting that rs35767 is related to the occurrence of T2DM. A total of 5 gene interaction models was obtained through analyzing the interaction of 5 SNP loci with the GMDR method. Among them, the two-factor model that included rs35767 locus and rs5742694 locus had statistical difference with a large cross-validation consistency (10/10). The combination of GG/CC, GA/AA, AA/AA, and AA/AC genotype was in high-risk group, whereas the combination of GG/AA, GG/AC, GA/AC and GA/CC genotype was in the low-risk group. The risk of T2DM in the high-risk group was 2.165 times than that of the low-risk group (OR = 2.165, 95% CI = 1.478-3.171). CONCLUSION: TG, HDL, LDL, BUN, and Cr are influencing factors of T2DM in Uyghur population. The rs35767 locus of IGF-1 gene may be associated with T2DM in Uyghur population. The high-risk group composing of rs35767 locus and rs5742694 locus has a higher risk of T2DM.

Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury.

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality in adults under 40 years old. Once primary injury occurs after TBI, neuroinflammation and oxidative stress (OS) are triggered, contributing to the development of many TBI-induced neurological deficits, and reducing the probability of critical trauma patients´ survival. Regardless the research investment on the development of anti-inflammatory and neuroprotective treatments, most pre-clinical studies have failed to report significant effects, probably because of the limited blood brain barrier permeability of no-steroidal or steroidal anti-inflammatory drugs. Lately, neurotrophic factors, such as the insulin-like growth factor 1 (IGF-1), are considered attractive therapeutic alternatives for diverse neurological pathologies, as they are neuromodulators linked to neuroprotection and anti-inflammatory effects. Considering this background, the aim of the present investigation is to test early IGF-1 gene therapy in both OS markers and cognitive deficits induced by TBI. Male Wistar rats were injected via Cisterna Magna with recombinant adenoviral vectors containing the IGF-1 gene cDNA 15 min post-TBI. Animals were sacrificed after 60 min, 24 h or 7 days to study the advanced oxidation protein products (AOPP) and malondialdehyde (MDA) levels, to recognize the protein oxidation damage and lipid peroxidation respectively, in the TBI neighboring brain areas. Cognitive deficits were assessed by evaluating working memory 7 days after TBI. The results reported significant increases of AOPP and MDA levels at 60 min, 24 h, and 7 days after TBI in the prefrontal cortex, motor cortex and hippocampus. In addition, at day 7, TBI also reduced working memory performance. Interestingly, AOPP, and MDA levels in the studied brain areas were significantly reduced after IGF-1 gene therapy that in turn prevented cognitive deficits, restoring TBI-animals working memory performance to similar values regarding control. In conclusion, early IGF-1 gene therapy could be considered a novel therapeutic approach to targeting neuroinflammation as well as to preventing some behavioral deficits related to TBI.

Combined therapy of adenovirus vector mediated IGF-1 gene with anti-CD20 mAbs exerts potential beneficial role on type 1 diabetes in nonobese diabetic mice.

AIMS: To assess the protective effects of combined treatment with anti-CD20 monoclonal antibody (mAb) and adenovirus mediated mouse insulin-like growth factor 1 (Adv-mIGF-1) gene on type 1 diabetes (T1D) in nonobese diabetic (NOD) mice at early stage. METHODS: To simultaneously restore the proportion of Th cells and block the interaction of B cells, NOD model mice were assigned to four groups which received PBS, Adv-mIGF-1 gene and anti-CD20 mAbs alone or combination, respectively. After 16 weeks of therapeutic intervention, blood samples and pancreatic tissues of mice were measured via the methods of ELISA, RT-PCR, western blotting, H&E staining, TUNEL and immunohistochemistry assays. KEY FINDINGS: Chronic combination intervention with Adv-mIGF-1 gene and anti-CD20 mAbs reduced the T1D-related morbidity, promoted the secretion of insulin, controlled the blood glucose levels (BGLs) and alleviated insulitis of experimental mice. In addition, current combination intervention also protected the pancreatic ß cells via suppressing the expression of Fas and TNF-α, inhibiting Caspase-3/8 related apoptotic pathway, and activating the Bcl-2-related antiapoptotic pathway. Furthermore, current combination therapy also increased the expression levels of PDX-1 and CK-19 genes, and finally accelerated the proliferation and differentiation of pancreatic ß-cells. In addition, combination therapy could also ameliorate the pathological characteristics of diabetic nephropathy in NOD mice. CONCLUSION: Combination treatment with Adv-mIGF-1 gene and anti-CD20 mAbs may exert a potential beneficial role on T1D in NOD mice.

Tissue expression profile, polymorphism of IGF1 gene and its effect on body size traits of Dezhou donkey.

Insulin-like growth factor 1 (IGF1) is a multifunctional cell proliferation regulator that plays a critical role in regulating animal growth and development. In this study, the expression level of IGF1 gene in different tissues of Dezhou donkey in different periods was investigated by RT-qPCR. Meanwhile, two mutation sites were identified within the IGF1 gene and its effect on body size traits of Dezhou donkey was analysed. The results showed that the expression level of the adult donkey IGF1 gene in heart, liver, spleen, lung, renal and gastric tissues is higher than that of the young donkeys, but the young donkeys are significantly higher in muscle tissues than the adult donkeys. The IGF1-1 and IGF1-2 loci showed a trend that the GG mutant was larger than other genotypes in the growth traits of both male and female donkeys, among which the IGF1-1 loci had a significant association with the chest circumference and chest depth of male donkeys (P < 0.05), and the IGF1-2 loci had a significant association with the chest circumference of female donkeys. Haplotype combination Hap1Hap1 (GG-GG) showed a greater tendency than Hap2Hap2 (AA-GG) combination in terms of growth traits, reflecting that the results were consistent with the analysis results of genotypes, which also proved the analysis results of genotypes and growth traits had certain reliability. In summary, the IGF1 gene is a candidate gene for growth and development, and its polymorphisms can be used as the molecular markers for Dezhou donkey breeding.

Association of insulin-like growth factor 1 (IGF1) gene polymorphism with the reproductive performance of three dual-purpose chicken breeds.

The study was designed to investigate the association of Insulin-like growth factor 1 (IGF1) gene polymorphism with the reproductive performance of FUNAAB-Alpha, Sasso, and Kuroiler dual-purpose chicken breeds. To achieve this, a total of 250 healthy hens were selected at 12 wk of age and were intensively managed in cages for 52 wk. Blood sample was taken from each chicken at the 34th week and genomic DNA was extracted using Qiagentm DNA extraction kit, PCR was used to amplify the DNA fragments, and the PCR products were electrophoresed. Amplicons obtained were digested with restriction enzyme hinf1, and were further electrophoresed on 1.5% agarose gel. Data obtained were analyzed using the General linear model of SAS (2002) version 9.0 to determine the effect of IGF1 gene polymorphism and the distribution of alleles within the breeds. Results show polymorphism of the IGF1 gene and the restriction analysis indicated two alleles; A 58% and C 42% with the identification of genotypes AA, AC, and CC, and genotypic frequency of 22%, 43%, and 35%, respectively. Significant associations were observed between the polymorphism of the IGF1 gene, age of the bird at first lay, and weight of the hen at first lay. Chickens with haplotype CC came earlier into lay compared to those with the other two haplotypes (AA and AC). Therefore, the study suggests that haplotype CC could be used as a genetic marker to select for an improved laying performance in chickens.

Polymorphism of insulin-like growth factor 1 gene and its relationship with reproductive performances and milk yield in Sarda dairy sheep.

The aim of this research was to detect polymorphisms within the IGF-I gene in dairy sheep and to verify their influence on milk yield and reproductive performances. Four hundred Sarda ewes in their second lactation were selected from 2 farms. Their reproductive traits (fertility rate, interval in days from ram introduction to lambing and litter size) and milk yield were recorded, from the second to the fourth lactation. DNA was extracted from individual blood samples and subjected to amplification and sequencing of the IGF-I gene 5' UTR and Exon 3 regions. Three polymorphic sites were recorded at positions g184028491C>G and g184028489C>T of the 5'UTR, and g184023223G>A of the Exon 3. The C allele at position g184028491 showed a significant association with higher fertility rate (P < 0.05) and a shorter interval in days from ram introduction to lambing (P < 0.01). In addition, a significant effect of the CC genotype was found with higher milk yield for P < 0.05 in the second and third lactation, and P < 0.01 in the fourth lactation compared to the other genotypes. Even, AA genotype at position g184023223 of the exon 3 showed a positive significant effect on milk yield for P < 0.05, in the second and third lactation, and for P < 0.01 in fourth lactation compared to the other genotypes. In conclusion the found SNPs showed a significant influence on reproductive performances and milk yield in Sarda sheep breed suggesting a possible application in sheep selection plans.

Effect of miR-152-3p-targeted IGF1 gene on high glucose-induced activity and apoptosis of ARPE-19 cells / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the effect of microRNA-152-3p(miR-152-3p)targeting insulin-like growth factor 1(IGF1)gene on high glucose-induced retinal pigment epithelial ARPE-19 cell activity and apoptosis, and to explore its role mechanism. <p>METHODS: High glucose was induced into ARPE-19 cells and transfected with miR-152-3p mimics. MTT assay was used to detect cell proliferation activity. Flow cytometry was used to detect apoptosis. Fluorescence quantitative PCR(RT-PCR)was used to detect cells. The expression levels of IGF1 and VEGF in the cells were detected by Western blot and the binding relationship between IGF1 and miR-152-3p was detected by the dual luciferase reporter gene.<p>RESULTS:High glucose can decrease the activity of ARPE-19 cells, increase the apoptosis rate, inhibit the expression of miR-152-3p and increase the expression of IGF1 and VEGF. Over expression of miR-152-3p can up-regulate high glucose-induced cells. Increased activity and increased apoptosis inhibited the expression of IGF1 and VEGF. The dual luciferase reporter gene assay verified that IGF1 is the target gene of miR-152-3p.<p>CONCLUSION: miR-152-3p can inhibit the inhibition of high glucose-induced ARPE-19 cell activity and increase apoptosis by targeting IGF1 gene.

Investigation of the 5' flanking region and exon 3 polymorphisms of IGF-1 gene showed moderate association with semen quality in Sanjabi breed rams.

In this study, semen samples were collected from 96 Sanjabi rams in order to investigate the IGF-1 gene polymorphisms and their relationship with the characteristics of semen quality and testicular size. The dimensions of scrotal length, width and circumference were measured during autumn and spring over two years. Blood samples were simultaneously collected from jugular vein to extract DNA. PCR was performed using specific primers to amplify 294 and 272bp fragments including 5' regulatory region and exon 3 of IGF-1 gene, respectively. PCR products were digested by BFOI and Eco88l restriction enzymes, respectively. Two genotypes including AA (194 and 100bp), AB (294, 194 and 100bp) and all possible genotypes including CC (182 and 90bp), CT (272, 182, and 90bp) and TT (272bp) were observed for 5' flanking region and exon 3 of IGF-1 gene, respectively. The significant differences among IGF-1 genotypes for testicular dimensions were not observed. However, the polymorphism of 5' flanking region in the studied population had significant effect on individual motility and percent morphology traits. Animals with AB genotype had significantly higher individual motility compared with AA genotype (P < 0.05). Also, animals with AA genotype had significantly the highest percent morphology compared with AB genotype (P < 0.1). The exon 3 of IGF-1 gene had significant effect on individual motility, concentration, morphology and water test traits. Animals with CT genotype had the highest sperm concentration (P < 0.1) and water test (P < 0.05) compared to CC and TT genotypes. Moreover, animals with TT genotype had significantly the highest percent morphology compared with other genotypes (P < 0.05). Briefly, the results indicated that individual motility, concentration, percent morphology and water test traits could be in association with IGF-1 genotypes. It might be concluded that polymorphisms in IGF-1gene can be considered to develop male fertility in future and for using in selection process of better animals under masker assisted selection programs.

New polymorphism in the 5' flanking region of IGF-1 gene and its association with wool traits in Egyptian Barki sheep.

Insulin-like growth factor-1 gene (IGF-1) is considered as a major candidate gene for the economic traits of animal production. Polymorphism of 5' flanking region of IGF-1 gene in Barki sheep (n = 91) and its association with wool traits were studied using the polymerase chain reaction coupled with single-strand conformation polymorphism technique (PCR-SSCP), PCR-restriction fragment length polymorphism (PCR-RFLP), sequence analysis and different measurements of wool traits (clean fleece weight and fiber diameter). PCR-SSCP analysis revealed three different banding patterns corresponding with three genotypes frequencies GG (0.25), GA (0.58), AA (0.17). PCR-RFLP and corresponding sequence analysis revealed nucleotide transversion from Guanine (G) to Cytosine (C) at nucleotide position 85 and transition from (G) to Adenine (A) at position 87. This is the first study that recorded two SNPs within the 5' flanking region of IGF-1 gene in Egyptian Barki sheep, which were submitted to DNA Data Bank OF Japan (DDBJ) with Accession No. LC151463.1. The genotype GG showed positive significant association (P < 0.001) with clean fleece weight (CFW) trait (Odd Ratio = 2.83). By contrast, genotype AA had negative significant association (P < 0.05) with such trait (Odd Ratio = 0.15). On the other hand, fiber diameter (FD) measurements showed no significant association (P > 0.05) with different IGF-1 genotypes. This study adds evidence of the association between IGF-1 gene polymorphism and CFW of wool in Egyptian Barki sheep. Therefore; it is important to consider IGF-1 gene as a candidate gene marker for wool weight traits and it should be identified before using successful breeding program.

A polymorphic repeat in the IGF1 promoter influences the risk of endometrial cancer.

Due to the lack of high-throughput genetic assays for tandem repeats, there is a paucity of knowledge about the role they may play in disease. A polymorphic CA repeat in the promoter region of the insulin-like growth factor 1 gene (IGF1 has been studied extensively over the past 10 years for association with the risk of developing breast cancer, among other cancers, with variable results. The aim of this study was to determine if this CA repeat is associated with the risk of developing breast cancer and endometrial cancer. Using a case-control design, we analysed the length of this CA repeat in a series of breast cancer and endometrial cancer cases and compared this with a control population. Our results showed an association when both alleles were considered in breast and endometrial cancers (P=0.029 and 0.011, respectively), but this did not pass our corrected threshold for significance due to multiple testing. When the allele lengths were analysed categorically against the most common allele length of 19 CA repeats, an association was observed with the risk of endometrial cancer due to a reduction in the number of long alleles (P=0.013). This was confirmed in an analysis of the long alleles separately for endometrial cancer risk (P=0.0012). Our study found no association between the length of this polymorphic CA repeat and breast cancer risk. The significant association observed between the CA repeat length and the risk of developing endometrial cancer has not been previously reported.

Effect of Taekwondo Training on Physical Fitness and Growth Index According to IGF-1 Gene Polymorphism in Children.

This study analyzed the effect of regular Taekwondo training for 16 weeks on physical fitness and growth index depending on different IGF-1 gene polymorphisms. The subjects of the study were 44 male students who were 8 year years old. The IGF-1 gene showed the highest frequency of 18 CA repeat (190 bp) in 50% of subjects, and was found in the homozygote (n=11), heterozygote (n=22) and non-carriers (n=11). The results of the physical fitness and growth index among the gene polymorphism groups indicated no significant differences but the expected height of the non-carrier group was significantly high (p<0.05). After Taekwondo training, the homozygote group and the non-carrier groups demonstrated significant (p<0.05) increase in grip strength and in time in the standing with one leg while closing eyes test, respectively. Only the homozygote group had a significant (p< 0.05) increase in thigh circumference. IGF-1 concentration significantly (p<0.05) increased in the heterozygote group, while HOMA-IR significantly (p<0.05) decreased in the homozygote group. Furthermore, there was a significant (p<0.05) decrease in glucose in both the homozygote and the non-carriers groups. The difference between physical fitness and growth index depending on the IGF-1 gene polymorphism after Taekwondo training did not show consistent impact.

A microsatellite polymorphism in IGF1 gene promoter and timing of natural menopause in Caucasian women.

BACKGROUND: Genes involved in the IGF-1 aging pathways in the human ovary can be considered strong candidates for predictors of the natural menopause timing. This study evaluates the association between a cytosine-adenine (CA) microsatellite polymorphism in the IGF1 gene promoter P1 and age at natural menopause. METHODS: Genomic DNA was extracted from the peripheral blood, PCR was performed using primers designed to amplify the polymorphic (CA) n repeat of the human IGF1 gene, an allele dose effect for the most common (CA)19 repeats allele, Cox proportional hazard regression models and the Kaplan-Meier cumulative survivorship method with the log-rank test were used to determine statistical significance of studied associations in a sample of 257 Polish women aged 40-58 years. RESULTS: Crude Cox proportional hazard regression analysis confirmed the association between the IGF1 gene polymorphism and the menopause timing (p=0.038). This relationship remained statistically significant after controlling for other menopause confounders in multivariate modelling. Out of the input variables, the (CA)n polymorphism in the IGF1 gene promoter, age at menarche and smoking status were independent covariates of the natural menopause timing (χ2=12.845; df=3; p=0.034). The onset of menopause at a younger age was likely associated with the IGF1 genotype variant not carrying the (CA)19 repeats allele, menarche before the age of 12 and a current cigarette smoker status (HR=1.6). CONCLUSION: This study provides evidence that a common cytosine-adenine (CA) microsatellite repeat polymorphism in the P1 promoter region of the IGF1 gene is an independent predictive factor for age at natural menopause in Caucasian women also after adjusting for other menopause covariates.

Effect of Taekwondo Training on Physical Fitness and Growth Index According to IGF-1 Gene Polymorphism in Children

This study analyzed the effect of regular Taekwondo training for 16 weeks on physical fitness and growth index depending on different IGF-1 gene polymorphisms. The subjects of the study were 44 male students who were 8 year years old. The IGF-1 gene showed the highest frequency of 18 CA repeat (190 bp) in 50% of subjects, and was found in the homozygote (n=11), heterozygote (n=22) and non-carriers (n=11). The results of the physical fitness and growth index among the gene polymorphism groups indicated no significant differences but the expected height of the non-carrier group was significantly high (p<0.05). After Taekwondo training, the homozygote group and the non-carrier groups demonstrated significant (p<0.05) increase in grip strength and in time in the standing with one leg while closing eyes test, respectively. Only the homozygote group had a significant (p< 0.05) increase in thigh circumference. IGF-1 concentration significantly (p<0.05) increased in the heterozygote group, while HOMA-IR significantly (p<0.05) decreased in the homozygote group. Furthermore, there was a significant (p<0.05) decrease in glucose in both the homozygote and the non-carriers groups. The difference between physical fitness and growth index depending on the IGF-1 gene polymorphism after Taekwondo training did not show consistent impact.