👤 Roya Kelishadi

Metabolic syndrome (MetS) is a complex and multifactorial disorder characterized by insulin resistance, dyslipidaemia, hyperglycemia, abdominal obesity, and elevated blood pressure. The apolipoprotein A5 (APOA5) gene variants have been reported to correlate with two major components of MetS, including low levels of high density lipoprotein cholesterol (HDL-C) and high levels of triglyceride. In the present study, we explored the associations between five single nucleotide polymorphisms (SNPs) of APOA5 gene and the MetS risk. In a case-control design, 120 Iranian children and adolescents with/without MetS were genotyped by polymerase chain reaction-sequencing for these SNPs. Then, we investigated the association of SNPs, individually or in haplotype constructs, with MetS risk. The rs34089864 variant and H1 haplotype (harboring the two major alleles of rs619054 and rs34089864) were associated with HDL-C levels. However, there was no significant association between different haplotypes/individual SNPs and MetS risk. These results presented no association of APOA5 3'UTR SNPs with MetS. Further studies, including other polymorphisms, are required to investigate the involvement of APOA5 gene in the genetic susceptibility to MetS in the pediatric age group. Show less

In this study, we aimed to assess the association between four variants in three genes whose association has been reported in adults but not in children. We evaluated the relationship of the GCKR (rs780094), GCKR (rs1260333), FADS (rs174547), and MLXIPL (rs3812316) polymorphisms with serum lipid levels in Iranian children. This cross-sectional study was conducted in a subpopulation of the CASPIAN III study. During this study, 550 frozen whole blood samples were selected randomly. Using the recorded information of selected cases, those with and without abnormal lipid levels were determined. Allelic and genotypic frequencies of GCKR (rs780094), GCKR (rs1260333), MLXIPL (rs3812316), and FADS (rs174547) polymorphisms were determined and compared in dyslipidemic and normal children. The association between the studied polymorphisms and lipid profiles was determined using logistic regression analysis. Prevalence of hypercholesterolemia, hypertriglyceridemia, high low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C) were 24.9, 34.5, 19.0, and 40.7%, respectively. Significant correlations were found between GCKR (rs780094) and GCKR (rs1260333) polymorphisms and cholesterol and triglyceride levels, between FADS (rs174547) polymorphism and level of triglyceride, and also between MLXIPL (rs3812316) and levels of HDL-C. The results of this population-based study provide evidence for a relationship between lipid regulatory gene polymorphisms including GCKR (rs780094), GCKR (rs1260333), FADS (rs174547), and MLXIPL (rs3812316) with dyslipidemia in an Iranian population. These results could provide baseline information on as well as further insight into the genetic makeup of lipid profiles in Iranian children, which could be used for preventative strategies. Show less

Genetically, predisposed children are considered as at-risk individuals for cardiovascular disease. In this study, we aimed to compare the frequency of four-lipid regulatory polymorphism in obese and normal-weight children with and without cardiometabolic risk factors. In this nested case-control study, 600 samples of four groups of participants consisted of those with normal weight with and without cardiometabolic risk factors and obese with and without cardiometabolic risk factors. Allelic and genotypic frequencies of GCKR (rs780094), GCKR (rs1260333), MLXIPL (rs3812316), and FADS (rs174547) polymorphisms were compared in the four studied groups. Data of 528 samples were complete and included in this study. The mean (standard deviation) age of participants was 15.01 (2.21) years. Frequency of tt allele (minor allele) of GCKR (rs1260333) polymorphism was significantly lower in normal weight metabolically healthy participants than metabolically unhealthy normal weight (MUHNW) and obese children with and without cardiometabolic risk factor ( The findings of our study indicated that the minor allele of GCKR (rs1260333) single nucleotide polymorphisms (SNPs) could have pathogenic effect for obesity and cardiometabolic risk factors. Ga allele of GCKR (rs780094) SNPs had a protective effect on obesity. Minor alleles of MLXIPL (rs3812316) could have a protective effect for obesity and cardiometabolic risk factors. Show less

Metabolic syndrome (MetS) is a common disorder which is a constellation of clinical features including abdominal obesity, increased level of serum triglycerides (TGs) and decrease of serum high-density lipoprotein-cholesterol (HDL-C), elevated blood pressure, and glucose intolerance. The apolipoprotein A5 (APOA5) is involved in lipid metabolism, influencing the level of plasma TG and HDL-C. In the present study, we aimed to investigate the associations between four INDEL variants of APOA5 gene and the MetS risk. In this case-control study, we genotyped 116 Iranian children and adolescents with/without MetS by using Sanger sequencing method for these INDELs. Then, we explored the association of INDELs with MetS risk and their clinical components by logistic regression and one-way analysis of variance analyses. We identified a novel insertion polymorphism, c. *282-283 insAG/c. *282-283 insG variant, which appears among case and control groups. rs72525532 showed a significant difference for TG levels between various genotype groups. In addition, there were significant associations between newly identified single-nucleotide polymorphism (SNP) and rs72525532 with MetS risk. These results show that rs72525532 and the newly identified SNP may influence the susceptibility of the individuals to MetS. Show less

In the present study, we evaluated the association of rs662799 variant of the APOA5 gene with Metabolic syndrome (MetS) in a sample of children and adolescents from Isfahan. This case control study comprised 50 cases of MetS and 50 controls. Mismatched polymerase chain reaction-restriction fragment length polymorphism (mPCR-RFLP) was used to genotype -1131T>C polymorphism. Findings : No significant association was documented for APOA5 genotypes with the measured laboratory parameters for CC, CT, and TT genotypes in the two groups studied. By logistic regression using a dominant model, the odds ratio (95% confidence interval0 for the MetS was 0.38 (0.139-1.0350 and 0.29 (0.08-1.071 for the unadjusted and adjusted models, respectively. This study suggests that among studied children and adolescents, -1131T>C polymorphism in the APOA5 gene may not be a major contributor to the MetS risk. Show less

Depressed high-density lipoprotein cholesterol (HDL-C) is prevalent the Middle East and North Africa. Some studies have documented associations between HDL-C and several single nucleotide polymorphisms (SNPs) in candidate gene polymorphisms. We investigated the associations between SNP genotypes and HDL-C levels in Iranian students, aged 10-18 years. Genotyping was performed in 750 randomly selected participants among those with low HDL-C levels (below 5th percentile), intermediate HDL-C levels (5-95th) and high HDL-C levels (above the 95th percentile). Minor allele frequencies (MAFs) of the SNPs of interest were compared between the three HDL-C groups. The vast majority of pairwise comparisons of MAFs between HDL-C groups were significant. Pairwise comparisons between low and high HDL-C groups showed significant between-group differences in MAFs for all SNPs, except for APOC3 rs5128. Pairwise comparisons between low and intermediate HDL-C groups showed significant between-group differences in MAFs for all SNPs, except for APOC3 rs5128 and APOA1 rs2893157. Pairwise comparisons between intermediate and high HDL-C groups showed significant between-group differences in MAFs for all SNPs, except for ABCA1 APOC3 rs5128 and APOA1 rs2893157. After adjustment for confounding factors, including age, sex, body mass index, low physical activity, consumption of saturated fats, and socioeconomic status, ABCA1 r1587K and CETP A373P significantly increased the risk of depressed HDL-C, and CETP Taq1 had a protective role. This study replicated several associations between HDL-C levels and candidate gene SNPs from genome-wide associations with HDL-C in Iranians from the pediatric age group. Show less