Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome

Background The objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH). Methods This was a case-control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome variables, SNP and haplotype frequencies were compared between control (n = 155) and OHSS (n = 19) groups. Results Patients who developed OHSS had significantly higher response markers (estradiol levels of the day of hCG administration, number of follicles developed, number of eggs retrieved) than control patients. When adjusted for age and self-identified race, the rs2305945 G/T genotype was associated (P = 0.027) with a decreased risk (OR = 0.30; 95% CI = 0.10, 0.93) of developing OHSS using an overdominant model. The rs2305945 G/T variant was also associated with decreased COH response (number of follicles, number of eggs retrieved) in an overdominant model. The rs2305948, rs1870378, rs2305945 (C-T-G) haplotype was associated with both decreased COH response and OHSS risk (unadjusted OR = 0.10; 95% CI = 0.01, 0.80, P = 0.031). Conclusions The KDR receptor is believed to play a central role OHSS development and is a target for pharmacological prevention of OHSS. These results indicate that genetic variation in the KDR gene may impact individual risk of developing OHSS from COH. In addition, the rs2305948 SNP and C-T-G haplotype might serve as potential biomarkers for poor ovarian response to COH

MC4R Variant Is Associated With BMI but Not Response to Resistance Training in Young Females

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93697/1/oby_2147_sm_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93697/2/oby.2010.180.pd

INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men

Background A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G\u3eC, Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population. Methods We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18–40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test. Results Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 ± 5713 mm3 vs. GC/CC: n = 181; 268521 ± 5003 mm3; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% ± 1.74% vs. GC/CC: n = 93; 6.39% ± 1.82%; p = 0.035). Conclusion Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation

Ccl2 And Ccr2 Variants Are Associated With Skeletal Muscle Strength And Change In Strength With Resistance Training

Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation. Copyright © 2010 the American Physiological Society

Slc30A8 Nonsynonymous Variant Is Associated With Recovery Following Exercise And Skeletal Muscle Size And Strength

Genome-wide association studies have identified thousands of variants that are associated with numerous phenotypes. One such variant, rs13266634, a nonsynonymous single nucleotide polymorphism in the solute carrier family 30 (zinc transporter) member eight gene, is associated with a 53% increase in the risk of developing type 2 diabetes (T2D). We hypothesized that individuals with the protective allele against T2D would show a positive response to short-term and long-term resistance exercise. Two cohorts of young adults-the Eccentric Muscle Damage (EMD; n = 156) cohort and the Functional Single Nucleotide Polymorphisms Associated with Muscle Size and Strength Study (FAMuSS; n = 874)-were tested for association of the rs13266634 variant with measures of skeletal muscle response to resistance exercise. Our results were sexually dimorphic in both cohorts. Men in the EMD study with two copies of the protective allele showed less post-exercise bout strength loss, less soreness, and lower creatine kinase values. In addition, men in the FAMuSS, homozygous for the protective allele, showed higher pre-exercise strength and larger arm skeletal muscle volume, but did not show a significant difference in skeletal muscle hypertrophy or strength with resistance training. © 2014 by the American Diabetes Association

Mc4R Variant Is Associated With Bmi But Not Response To Resistance Training In Young Females

Recently, a genome-wide association study (GWAS) that identified eight single-nucleotide polymorphisms (SNPs) associated with BMI highlighted a possible neuronal influence on the development of obesity. We hypothesized these SNPs would govern the response of BMI and subcutaneous fat to resistance training in young individuals (age = 24 years). We genotyped the eight GWAS-identified SNPs in the article by Willer et al. in a cohort (n = 796) that undertook a 12-week resistance-training program. Females with a copy of the rare allele (C) for rs17782313 (MC4R) had significantly higher BMIs (CC/CT: n = 174; 24.70 ± 0.33 kg/m2, TT: n = 278; 23.41 ± 0.26 kg/m2, P = 0.002), and the SNP explained 1.9% of overall variation in BMI. Males with a copy of the rare allele (T) for rs6548238 (TMEM18) had lower amounts of subcutaneous fat pretraining (CT/TT: n = 65; 156,534 ± 7,415 mm3, CC: n = 136; 177,825 ± 5,139 mm3, P = 0.019) and males with a copy of the rare allele (A) for rs9939609 (FTO) lost a significant amount of subcutaneous fat with exercise (AT/AA: n = 83; -798.35 ± 2,624.30 mm3, TT: n = 47; 9,435.23 ± 3,494.44 mm 3, P = 0.021). Females with a copy of the G allele for a missense variant in the SH2B1 (rs7498665) was associated with less change of subcutaneous fat volume with exercise (AG/GG: n = 191; 9,813 ± 2,250 mm3 vs. AA: n = 126; 770 ± 2,772 mm3; P = 0.011). These data support the original finding that there is an association between measures of obesity and a variant near the MC4R gene and extends these results to a younger population and implicates FTO, TMEM18, and SH2B1 polymorphisms in subcutaneous fat regulation. © 2010 The Obesity Society

Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome

Background: The objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH).Methods: This was a case-control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome variables, SNP and haplotype frequencies were compared between control (n = 155) and OHSS (n = 19) groups.Results: Patients who developed OHSS had significantly higher response markers (estradiol levels of the day of hCG administration, number of follicles developed, number of eggs retrieved) than control patients. When adjusted for age and self-identified race, the rs2305945 G/T genotype was associated (P = 0.027) with a decreased risk (OR = 0.30; 95% CI = 0.10, 0.93) of developing OHSS using an overdominant model. The rs2305945 G/T variant was also associated with decreased COH response (number of follicles, number of eggs retrieved) in an overdominant model. The rs2305948, rs1870378, rs2305945 (C-T-G) haplotype was associated with both decreased COH response and OHSS risk (unadjusted OR = 0.10; 95% CI = 0.01, 0.80, P = 0.031).Conclusions: The KDR receptor is believed to play a central role OHSS development and is a target for pharmacological prevention of OHSS. These results indicate that genetic variation in the KDR gene may impact individual risk of developing OHSS from COH. In addition, the rs2305948 SNP and C-T-G haplotype might serve as potential biomarkers for poor ovarian response to COH. © 2014 O\u27Brien et al.; licensee BioMed Central Ltd

CCL2 and CCR2 variants are Associated with skeletal muscle strength and change in strength with resistance training

Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation. Copyright © 2010 the American Physiological Society

SLC30A8 nonsynonymous Variant is associated with recovery following exercise and skeletal muscle size and strength

Genome-wide association studies have identified thousands of variants that are associated with numerous phenotypes. One such variant, rs13266634, a nonsynonymous single nucleotide polymorphism in the solute carrier family 30 (zinc transporter) member eight gene, is associated with a 53% increase in the risk of developing type 2 diabetes (T2D). We hypothesized that individuals with the protective allele against T2D would show a positive response to short-term and long-term resistance exercise. Two cohorts of young adults-the Eccentric Muscle Damage (EMD; n = 156) cohort and the Functional Single Nucleotide Polymorphisms Associated with Muscle Size and Strength Study (FAMuSS; n = 874)-were tested for association of the rs13266634 variant with measures of skeletal muscle response to resistance exercise. Our results were sexually dimorphic in both cohorts. Men in the EMD study with two copies of the protective allele showed less post-exercise bout strength loss, less soreness, and lower creatine kinase values. In addition, men in the FAMuSS, homozygous for the protective allele, showed higher pre-exercise strength and larger arm skeletal muscle volume, but did not show a significant difference in skeletal muscle hypertrophy or strength with resistance training. © 2014 by the American Diabetes Association