1. No clinical utility of common polymorphisms in IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 genes previously associated with insulin resistance in overweight children from Romania and Moldova.
- Author
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Chirita-Emandi A, Munteanu D, Andreescu N, Tutac P, Paul C, Velea IP, Pusztai AM, Hlistun V, Boiciuc C, Sacara V, Vudu L, Usurelu N, and Puiu M
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adolescent, Body Mass Index, Case-Control Studies, Child, Child, Preschool, Co-Repressor Proteins, Female, Follow-Up Studies, Germinal Center Kinases, Humans, Insulin Receptor Substrate Proteins genetics, Insulin-Like Growth Factor I genetics, Male, Moldova epidemiology, Obesity epidemiology, PPAR gamma genetics, Pediatric Obesity epidemiology, Prognosis, Protein Serine-Threonine Kinases genetics, Repressor Proteins genetics, Romania epidemiology, Biomarkers analysis, Insulin Resistance genetics, Obesity genetics, Pediatric Obesity genetics, Polymorphism, Single Nucleotide
- Abstract
Background Previous genome-wide association studies (GWAS) identified IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 as candidate genes for insulin resistance and type 2 diabetes (T2D). We investigated the associations of these previously reported common variants in these genes with insulin resistance in overweight children from Romania and Moldova. Methods Six single nucleotide polymorphisms (SNPs), IGF1 (rs35767), IRS1 (rs2943634), GCKR (rs780094), PPARG (rs1801282), GCK1 (rs1799884) and KCTD15 (rs29941), were genotyped in 100 overweight children along with clinical and metabolic parameters. Homeostatic model assessment of insulin resistance (HOMA-IR) above 3.4 (defining insulin resistance) was used as the outcome. Results Children differed in insulin resistance status despite having similar body mass index (BMI) standard deviation scores (SDS) (World Health Organization, [WHO] reference). The identified predictors for altered insulin metabolism were higher cholesterol levels, higher diastolic blood pressure and higher waist-to-hip-ratio (as a marker for increased abdominal fat). None of the SNPs showed significant association with increase in the risk for insulin resistance in children (p range=0.478-0.724; odds ratio [OR] range=1.924-4.842); however, the risk allele in GCKR (rs780094, p=0.06, OR=6.871) demonstrated near statistical significance. Conclusions The interrogated risk alleles did not show any significant association with insulin resistance in children in our cohort; however, the GCKR (rs780094) might be a viable candidate in larger cohorts. The lack of replication of the proposed association may point to differences in linkage disequilibrium or effect modifiers across studies.
- Published
- 2019
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