Rybicka J, etal., Int J Cardiol. 2015 Sep 15;195:7-14. doi: 10.1016/j.ijcard.2015.05.077. Epub 2015 May 15.
BACKGROUND: High sensitivity troponin T (hsTnT) assays enable us to detect chronic heart failure (CHF). Adult congenital heart disease (ACHD) patients are classified as being in at least stage B of CHF. The purpose of the study was to assess hsTnT levels in ACHD patients and determine its clinical s
ignificance. METHODS: This is a prospective cross-sectional study. We assessed hsTnT in 131 ACHD patients and in 30 healthy controls. All ACHD patients underwent routine clinical and echocardiographic evaluation and had hsTnT and N-terminal brain natriuretic peptide (NT-pro-BNP) level measurements. RESULTS: The cut-off value defining an abnormal hsTnT level was established as >0.005 ng/mL. 35.1% (n=46) of ACHD patients had abnormal hsTnT compared to 6.7% (n=2) of healthy controls (p=0.002). The prevalence of elevated hsTnT did not differ between simple and complex and between non-cyanotic and cyanotic congenital heart disease (CHD). The sensitivity and specificity of hsTnT for the detection of moderate or severe (significant) systemic ventricular dysfunction was 78.6% and 69.8%, respectively (OR 8.49; CI 95% 2.23-32.30; p<0,0001) whereas for significant pulmonary ventricular dysfunction it was 66.7% and 68.2%, respectively (OR 4.29; CI 95% 1.56-11.79; p=0.003). In multivariate logistic regression models elevated hsTnT, but not NT-pro-BNP, was independently associated with both significant systemic ventricular dysfunction (p=0.004) and significant pulmonary ventricular dysfunction (p=0.011). CONCLUSIONS: A troponin leak is observed in a substantial number of ACHD patients and is associated with significant systemic and pulmonary ventricular impairment. Compared to NT-pro-BNP, hsTnT is a more specific independent predictor of ventricular dysfunction in ACHD.
Elert-Dobkowska E, etal., J Neurol Sci. 2015 Dec 15;359(1-2):35-9. doi: 10.1016/j.jns.2015.10.030. Epub 2015 Oct 17.
Hereditary spastic paraplegias (HSPs) consist of a heterogeneous group of genetically determined neurodegenerative disorders. Progressive lower extremity weakness and spasticity are the prominent features of HSPs resulting from retrograde axonal degeneration of the corticospinal tracts. Three geneti
c types, SPG3 (ATL1), SPG4 (SPAST) and SPG31 (REEP1), appear predominantly and may account for up to 50% of autosomal dominant hereditary spastic paraplegias (AD-HSPs). Here, we present the results of genetic testing of the three mentioned SPG genetic types in a group of 216 unrelated Polish patients affected with spastic paraplegia. Molecular evaluation was performed by multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing. Nineteen novel mutations: 13 in SPAST, 4 in ATL1 and 2 in REEP1, were identified among overall 50 different mutations detected in 57 families. Genetic analysis resulted in the identification of molecular defects in 54% of familial and 8.4% of isolated cases. Our research expanded the causative mutations spectrum of the three most common genetic forms of HSPs found in a large cohort of probands originating from the Central Europe.
Wang YF, etal., Sci Rep. 2015 Oct 27;5:15711. doi: 10.1038/srep15711.
Three high-density lipoprotein (HDL)-related loci have been reported to be associated with age-related macular degeneration (AMD), but the results were inconsistent. In this study, the cholesteryl ester transfer protein (CETP) rs3764261 variant was significantly associated with an increased risk of
AMD (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.05-1.21, P < 0.001), and the hepatic lipase (LIPC) rs10468017 variant was associated with a significantly decreased risk of AMD (OR = 0.81, CI: 0.76-0.86, P < 0.001). Individuals carrying the lipoprotein lipase (LPL) rs12678919 polymorphism (A --> G) had no significant change in the risk of developing AMD (OR = 1.01, CI: 0.92-1.10, P = 0.17). After adjusting for the complement factor H (CFH) gene, both CETP and LPL conferred a significantly increased AMD risk (ORCETP = 1.17, CI: 1.08-1.26, P < 0.001; ORLPL = 1.11, CI: 1.01-1.22, P = 0.02). Subgroup analysis based on ethnicity revealed a significant association between the CETP variant and AMD in both Americans (OR = 1.12, CI: 1.02-1.23, P = 0.01) and Europeans (OR = 1.10, CI: 1.01-1.19, P = 0.011). This meta-analysis revealed that both CETP rs3764261 and LIPC rs10468017 polymorphisms were significantly associated with AMD risk. After adjustment for the CFH gene, CETP/LPL conferred a significantly increased susceptibility to the disease, indicating potential interactions among genes in the complement system and the lipid metabolism pathway.
Hokanson JE, etal., Diabetes. 2002 Apr;51(4):1208-13.
Type 1 diabetes is associated with coronary heart disease (CHD) and coronary artery calcification (CAC), a measure of subclinical CHD. The hepatic lipase gene promoter polymorphism (LIPC-480C>T) is a common variant affecting lipid metabolism. This study examined
the relation between the LIPC-480C>T and CAC in type 1 diabetes. In the type 1 diabetic patients studied, 56% had CAC >0 Agatston units (AU). These subjects had a longer duration of diabetes (26.2 +/- 1.3 vs. 17.8 +/- 1.4 years; P < 0.001), lower HDL cholesterol levels (55.7 +/- 2.4 vs. 61.0 +/- 2.5 mg/dl; P = 0.05), higher triglyceride levels (101 +/- 17.3 vs. 66 +/- 7.6 mg/dl; P < 0.05), and higher diastolic blood pressure (79.7 +/- 1.0 vs. 76.0 +/- 1.4 mmHg; P < 0.05). The LIPC-480 T allele was more common in subjects with CAC (frequency = 0.31 +/- 0.05 vs. 0.14 +/- 0.04; P = 0.006). The proportion with CAC was 44% in LIPC-480CC subjects, 71% in heterozygotes, and 83% in LIPC-480TT subjects (P < 0.01). LIPC-480 T allele frequency increased as the amount of CAC increased (P = 0.007). LIPC-480 genotype was independently associated with the CAC (odds ratio = 2.90, 95% CI 1.22-6.92, P < 0.05) after adjusting for duration of diabetes, age, sex, diastolic blood pressure, HDL cholesterol, and triglyceride levels. In conclusion, the LIPC-480C>T polymorphism was associated with subclinical CHD in type 1 diabetes. This genetic variant may identify subjects in which early intervention to prevent CHD may be appropriate.
Park HS, etal., Sci Rep. 2020 Oct 1;10(1):16294. doi: 10.1038/s41598-020-73048-6.
The aim of this study was to identify novel genetic markers related to coronary artery disease (CAD) using a whole-exome sequencing (WES) approach and determine any associations between the selected gene polymorphisms and CAD prevalence. CUBN, HNF1A and LIPC gen
e polymorphisms related to CAD susceptibility were identified using WES screening. Possible associations between the five gene polymorphisms and CAD susceptibility were examined in 452 CAD patients and 421 control subjects. Multivariate logistic regression analyses indicated that the CUBN rs2291521GA and HNF1A rs55783344CT genotypes were associated with CAD (GG vs. GA; adjusted odds ratio [AOR] = 1.530; 95% confidence interval [CI] 1.113-2.103; P = 0.002 and CC vs. CT; AOR = 1.512; 95% CI 1.119-2.045; P = 0.007, respectively). The CUBN rs2291521GA and HNF1A rs55783344CT genotype combinations exhibited a stronger association with CAD risk (AOR = 2.622; 95% CI 1.518-4.526; P = 0.001). Gene-environment combinatorial analyses indicated that the CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotype combination and several clinical factors (fasting blood sugar (FBS), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels) were associated with increased CAD risk. The CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotypes in conjunction with abnormally elevated cholesterol levels increase the risk of developing CAD. This exploratory study suggests that polymorphisms in the CUBN, HNF1A, and LIPC genes can be useful biomarkers for CAD diagnosis and treatment.
Wang H, etal., J Cell Mol Med. 2015 Sep;19(9):2296-306. doi: 10.1111/jcmm.12663. Epub 2015 Aug 18.
Hepatic lipase (LIPC) is a key rate-limiting enzyme in lipoprotein catabolism pathways involved in the development of obesity. The C-514T polymorphism in the promoter region is associated with decreased LIPC activity. We per
formed a case-controlled study (850 obese children and 2119 controls) and evaluated the association between LIPC C-514T polymorphism, obesity and plasma lipid profile in Chinese children and adolescents. Additionally, we conducted a meta-analysis of all results from published studies as well as our own data. A significant association between the polymorphism and obesity is observed in boys (P = 0.042), but not in girls. And we observed a significant relationship of the polymorphism with total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) independent of obesity in boys. The T allele carriers have higher levels of low density lipoprotein cholesterol (LDL-C) in obese boys, and triglyceride (TG), TC and LDL-C in non-obese girls (all P < 0.05). In the meta-analysis, under dominant model the T allele increased body mass index (BMI) level in boys, while it decreased BMI in girls, and increased the levels of TC both in the overall and subgroups, TG and HDL-C in the overall and boys, and LDL-C in the overall (all P < 0.05). Our results suggest that the T allele might carry an increased risk of obesity in Chinese boys. The meta-analysis suggests that T allele acts as a risk allele for higher BMI levels in male childhood, while it is a protective allele in female childhood. And the polymorphism is associated with the levels of plasma lipids, which may be modulated by obesity and gender.
