A novel LMNA indel mutation identified in a family with atrioventricular block and atrial fibrillation.

ABSTRACT: It is well known that many genetic factors are involved in the occurrence and progression of atrioventricular block (AV block) and atrial fibrillation (AF). However, the genetic variants discovered so far have only explained parts of these processes. More genes and variants remain to be identified. In the present study, a three-generation family with an autosomal dominant form of AV block and AF was enrolled. Whole exome sequencing was conducted in three affected and one unaffected family member. A total of 64 nonsynonymous variants was shared by three affected individuals and not present in the unaffected individual. By selection of variants absent in the known databases and were predicted to be deleterious, 4 novel variants were identified. Only one novel frameshift insertion in the LMNA gene (c.825_826insCAGG) was identified in another affected family member and not detected in other non-affected family members and the 100 controls. Our finding expanded the spectrum of variants associated with AV block and AF, and was valuable in the genetic diagnosis of AV block and AF.

A previously unreported impact of a PLA2G7 gene polymorphism on the plasma levels of lipoprotein-associated phospholipase A2 activity and mass.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with the development of atherosclerosis. We aimed to assess the genetic determinants of Lp-PLA2 activity and mass by genotyping multiple polymorphisms in PLA2G7, the gene encoding Lp-PLA2, among 1258 participants from the Chinese Multi-provincial Cohort Study-Beijing Project. The Sequenom MassARRAY system, Taqman assay and direct sequencing were adopted. For the first time, the rs13218408 polymorphism was found to be significantly associated with reduced Lp-PLA2 levels. We also confirmed the significant association of previously validated polymorphisms (rs1421378, rs1805018, rs16874954 and rs2216465), even after adjusting for traditional cardiovascular risk factors and for Bonferroni correction. Percentages of variance attributable to rs13218408 were 7.2% for activity and 13.3% for mass, and were secondary to those of rs16874954 (8.1% for activity and 16.9% for mass). A significant joint effect of rs13218408 and rs16874954 was observed on Lp-PLA2 activity (P = 0.058) and mass (P = 0.003), with their minor alleles together linking to the largest reduction in Lp-PLA2 levels (37.8% reduction in activity and 41.6% reduction in mass). Taken together, our findings show a significant association of a PLA2G7 polymorphism with Lp-PLA2 levels, which was previously unreported in any population. The functionality of this genetic variation deserves further investigations.

Relationship between fine particulate air pollution and ischaemic heart disease morbidity and mortality.

OBJECTIVE: To assess the relationship between fine particulate matter (PM2.5) concentration and ischaemic heart disease (IHD) morbidity and mortality. METHODS: A time-series study conducted in Beijing from 1 January 2010 to 31 December 2012. Data on 369,469 IHD cases and 53,247 IHD deaths were collected by the Beijing Monitoring System for Cardiovascular Diseases, which covers all hospital admissions and deaths from IHD from Beijing's population of 19.61 million. RESULTS: The mean daily PM2.5 concentration was 96.2 µg/m(3) with a range from 3.9 to 493.9 µg/m(3). Only 15.3% of the daily PM2.5 concentrations achieved WHO Air Quality Guidelines target (25 µg/m(3)) in the study period. The dose-response relationships between PM2.5 and IHD morbidity and mortality were non-linear, with a steeper dose-response function at lower concentrations and a shallower response at higher concentrations. A 10 µg/m(3) increase in PM2.5 was associated with a 0.27% (95% CI 0.21 to 0.33%, p<2.00×10(-16)) increase in IHD morbidity and a 0.25% (95% CI 0.10 to 0.40%, p=1.15×10(-3)) increase in mortality on the same day. During the 3 years, there were 7703 cases and 1475 deaths advanced by PM2.5 pollution over expected rates if daily levels had not exceeded the WHO target. CONCLUSIONS: PM2.5 concentration was significantly associated with IHD morbidity and mortality in Beijing. Our findings provide a rationale for the urgent need for stringent control of air pollution to reduce PM2.5 concentration.

A meta-analysis of red yeast rice: an effective and relatively safe alternative approach for dyslipidemia.

OBJECTIVE: To explore whether red yeast rice is a safe and effective alternative approach for dyslipidemia. METHODS: Pubmed, the Cochrane Library, EBSCO host, Chinese VIP Information (VIP), China National Knowledge Infrastructure (CNKI), Wanfang Databases were searched for appropriate articles. Randomized trials of RYR (not including Xuezhikang and Zhibituo) and placebo as control in patients with dyslipidemia were considered. Two authors read all papers and independently extracted all relevant information. The primary outcomes were serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). The secondary outcomes were increased levels of alanine transaminase, aspartate aminotransferase, creatine kinase, creatinine and fasting blood glucose. RESULTS: A total of 13 randomized, placebo-controlled trials containing 804 participants were analyzed. Red yeast rice exhibited significant lowering effects on serum TC [WMD = -0.97 (95% CI: -1.13, -0.80) mmol/L, P<0.001], TG [WMD = -0.23 (95% CI: -0.31, -0.14) mmol/L, P<0.001], and LDL-C [WMD = -0.87 (95% CI: -1.03, -0.71) mmol/L, P<0.001] but no significant increasing effect on HDL-C [WMD = 0.08 (95% CI: -0.02, 0.19) mmol/L, P = 0.11] compared with placebo. No serious side effects were reported in all trials. CONCLUSIONS: The meta-analysis suggests that red yeast rice is an effective and relatively safe approach for dyslipidemia. However, further long-term, rigorously designed randomized controlled trials are still warranted before red yeast rice could be recommended to patients with dyslipidemia, especially as an alternative to statins.

Association between the lipoprotein-associated phospholipase A2 activity and the progression of subclinical atherosclerosis.

AIM: The lipoprotein-associated phospholipase A2(Lp-PLA2) level has been shown to be associated with the risk of clinical cardiovascular events. We aimed to investigate whether Lp-PLA2 is associated with the progression of subclinical atherosclerosis in the general population. METHODS: The degree of carotid plaque and the maximal intima-media thickness(IMT) were measured twice over a 5-year interval in 913 participants 45 to 74 years of age at baseline in a cohort study. The associations between the plasma Lp-PLA2 activity and the progression of carotid plaque and changes in the IMT level were assessed according to sex after adjusting for traditional risk factors and the high-sensitivity C-reactive protein(hsCRP) level. RESULTS: During the 5-year follow-up period, the progression of plaque was observed in 58.5% of men and 48.3% of women. The median maximal IMT level increased by 0.12 mm in men and 0.09 mm in women per year. The progression of plaque and changes in the IMT level increased according to the quartile of the Lp-PLA2 activity in men(p＜0.05 for trend), but not women. Following adjustment for traditional risk factors and the hsCRP level, the odds ratio for plaque progression associated with an increase in the Lp-PLA2 activity of one standard deviation was 1.28(95% CI=1.09-1.49, p=0.043) in men and 0.92(95% CI=0.78-1.08, p=0.273) in women. The regression coefficient for IMT progression was 0.003(p=0.004) in men and -0.001(p=0.166) in women after adjusting for the other factors. CONCLUSIONS: The Lp-PLA2 level is associated with the progression of subclinical atherosclerosis in men. Lp-PLA2 may play an important role in the pathogenesis of atherosclerosis and be a potential target for the early prevention of cardiovascular disease.

[Impact of gender on lipoprotein-associated phospholipase A2 activity and association with known cardiovascularrisk factors].

OBJECTIVE: To explore the impact of gender on lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity and association with known cardiovascular risk factors. METHODS: Participants in this study were recruited from Beijing sub-cohort from the Chinese Multi-provincial Cohort Study (CMCS) database. A total of 1471 participants with complete laboratory data were included in the study (688 male). Lp-PLA(2) activity was determined by colorimetric assay kit.Lp-PLA(2) activity level and correlation between Lp-PLA(2) activity and known risk factors were compared between men and women. RESULTS: (1) Lp-PLA(2) activity was higher in males than in females [(22.73 ± 8.52) nmol·min(-1)·ml(-1) vs.(20.01 ± 8.06) nmol·min(-1)·ml(-1), P < 0.01].(2) Age, waist circumference, systolic blood pressure, diastolic blood pressure and the prevalence of hypertension were higher in males than in females, while total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were higher in females than in males (P < 0.05 or P < 0.01).(3)Pearson correlation showed that Lp-PLA(2) activity was correlated with lipids ( total cholesterol, LDL-C, HDL-C, and triglyceride), blood pressure (systolic blood pressure and diastolic blood pressure), and adiposity associated parameters (waist circumference and body mass index) in males (all P < 0.01) and was correlated with lipid level (total cholesterol, LDL-C, HDL-C, and triglyceride) and age in females( P < 0.05 or P < 0.01). Correlations with variables associated with obesity or blood pressure in females were much weaker than those in males (in females, r = 0.02-0.08; in males, r = 0.10-0.16).(4)After adjustment for age, waist circumference, systolic blood pressure, glucose, LDL-C, HDL-C, triglyceride and high sensitivity C-reactive protein by multiple logistic regression model, Lp-PLA(2) activity was still significantly higher in males than in females (OR = 1.72, 95% confidence interval = 1.34-2.21, P < 0.01). CONCLUSIONS: Lp-PLA(2) activity and association with known cardiovascular risk factors differed in males and females. The gender difference in Lp-PLA(2) activity still presents after adjustment for known cardiovascular risk factors in this cohort.