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These data indicate that gene-gene and gene-environmental risk interactions form significant models in predicting early onset CAD.

Cardiovascular risk factors and atherosclerosis precursors were examined in 365 Turkish children and adolescents. Study participants were recruited at five different state schools. We tested single and multi-locus effects of six polymorphisms from five candidate genes, chosen based on prior known association with lipid levels in adults, for association with low ( £ 10 th percentile) high density lipoprotein cholesterol (HDL-C) and high ( ‡ 90 th percentile) triglycerides (TG), and the related continuous outcomes. We observed an association between CETP variant rs708272 and low HDL-C (allelic p = 0.020, genotypic p = 0.046), which was supported by an independent analysis, PRAT (PRAT control p = 0.027). Sex-stratified logistic regression analysis showed that the B2 allele of rs708272 decreased odds of being in the lower tenth percentile of HDL-C measurements (OR = 0.36, p = 0.02) in girls; this direction of effect was also seen in boys but was not significant (OR = 0.64, p = 0.21). Logistic regression analysis also revealed that the T allele of rs6257 (SHBG) decreased odds of being in the top tenth percentile of TG measurements in boys (OR = 0.43, p = 0.03). Analysis of lipid levels as a continuous trait revealed a significant association between rs708272 (CETP) and LDL-C levels in males ( p = 0.02) with the B2B2 genotype group having the lowest mean LDL-C; the same direction of effect was also seen in females ( p = 0.05). An effect was also seen between rs708272 and HDL-C levels in girls ( p = 0.01), with the B2B2 genotype having the highest mean HDL-C levels. Multi-locus analysis, using quantitative multifactor dimensionality reduction (qMDR) identified the previously mentioned CETP variant as the best single locus model, and overall model, for predicting HDL-C levels in children. This study provides evidence for association between CETP and low HDL-C phenotype in children, but the results appear to be weaker in children than previous results in adults and may also be subject to gender effects.

These three genetic polymorphisms are susceptibility loci and genotypes of these genes are neither necessary nor sufficient for the coronary artery disease to occur, but coexistence of high-risk alleles may increase the severity of coronary artery disease.

Hyperlipidemia is a major risk factor for coronary artery disease (CAD). Lipoprotein lipase (LPL) is an important enzyme in lipoprotein metabolism. S447X polymorphism of the LPL gene has been implicated in the pathogenesis of CAD. Carriers of X447 allele were reported to have lower triglyceride and higher high-density lipoprotein cholesterol levels as well as a reduced risk of CAD. We hypothesized that S447X gene polymorphism might have a protective effect for CAD. A total of 178 subjects (mean age 42.97 ± 6.5 years) who underwent coronary angiography for clinical indications were included in the study. The patients had been referred for evaluation of chest pain and/or abnormal stress tests, and were selected consecutively. Gensini scores were used to assess the severity of CAD; 97 patients were diagnosed with angiographically proven CAD, and 81 subjects did not display significant CAD (≥ 70%) angiographically. Genotyping of LPL S447X polymorphism was performed by real-time polymerase chain reaction amplification and fluorescent probe melting point analysis on the light cycler. The minor allele frequencies of LPL 447X allele were 11.1% and 6.2% among subjects without CAD compared with CAD subjects (P = 0.081) and 447X allele had favorable effects on lipid levels among CAD patients; 447X homozygotes and heterozygotes displayed lower total cholesterol (171 ± 37 vs 208 ± 48 mg/dl, P = 0.02), lower triglycerides (121 ± 72 vs 184 ± 86 mg/dl, P = 0.02), lower low-density lipoprotein cholesterol (102 ± 27 vs 129 ± 39 mg/dl, P = 0.03). Gensini scores were significantly lower among the heterozygotes and homozygotes of LPL 447X allele than in the LPL S447 homozygotes (15 ± 23 vs 25 ± 30, P = 0.048). S447X polymorphism of LPL gene may have a protective role for the severity of CAD. The beneficial effects of S447X polymorphism of the LPL gene may be through its favorable effects on lipid levels.

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Elevated triglycerides (TG) or low high density lipoprotein cholesterol (HDL-C) levels are common cardiometabolic risk factors in children. From a systems genetics standpoint, Visualization of Statistical Epistasis Networks (ViSEN) is a nonparametric entropy-based method that can characterize the global structure of interacting genetic factors. We identified a novel set of connected genetic and cardiometabolic risk factors with strong and significant interaction effects on two important dyslipidemia phenotypes (low HDL-C and high TG) in children and adolescents. Study participants were recruited from five schools in Istanbul, Turkey (n=360; 170 boys, 190 girls). Participants with TG levels≥75th and HDL-C levels≤25th percentile were defined as 'high TG' and 'low HDL-C', respectively. We genotyped participants for six single nucleotide polymorphisms (SNPs) in five genes with known associations to lipid levels (rs328 in LPL, rs708272 in CETP, rs1800588 in LIPC, rs1800977 in ABCA1, rs1799941 and rs6257 in SHBG gene). ViSEN was used to identify associations with dyslipidemia phenotypes. There were 71 (50 males, 21 females) and 93 (60 males and 33 females) subjects with low HDL-C and high TG, respectively. Biological variables including age, gender, and BMI were significantly associated with both phenotypes (p<0.001). Importantly, a single SNP, rs708272, was associated with low HDL-C (IG=2.24%, p=0.026). Pairwise and higher order interaction analyses in the full dataset for low HDL-C and high TG revealed the largest effects in the models containing rs1800977, rs708272, age (IG=6.20%, p=0.046) and rs1800588, age, BMI (IG, 3.06%, p=0.022), respectively. In conclusion, the present study brings us a step closer to a systems genetic approach in understanding lipid phenotypes in children. Further efforts can integrate population and laboratory-based studies, hence accelerate the preventive medicine efforts.

Background 17q12 microdeletion syndrome is a rare autosomal dominant chromosomal anomaly, caused by the deletion of a 1.4 Mb-spanning DNA sequence on the long arm of chromosome 17. Herein, we report the first bipolar disease (BPD) case with a 1.6-Mb deletion in the 17q11.2-17q12 chromosome region. Materials and methodsPhysical examination of the case was performed. Karyotype and microarray analyses were performed for the case and the parents. ResultsPhysical examination revealed mild dysmorphic features such as high and forehead, full cheeks, slightly depressed nasal bridge and arched eyebrow. Chromosomal analysis of the patient revealed 46, XX, del(17)(q12) karyotype, and parents' karyotype were normal. In the microarray analysis of patient, 1.6 megabases deletion was detected in the 17q12 region [arr(hg19) 17q12 (34,611,352-36,248,918) ×1]. The microarray analysis of the mother was normal. The father's microarray showed 473 kilobases duplication in the 11p11.12 region. ConclusionAlthough 17q12 deletion syndrome has been associated with bipolar disorder, very few such cases have been described in the literature. Genetic counseling should be considered in patients with remarkable phenotype, complex symptomatology, neurodevelopmental disorder and additional conspicuous medical conditions.