Age-related trends in lipid levels: a large-scale cross-sectional study of the general Chinese population.

OBJECTIVES: This study aimed to investigate the dynamic trends in total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels with ageing. DESIGN: A Chinese population-based cross-sectional study. SETTING: A physical examination centre of a general hospital. PARTICIPANTS: Adult subjects (178 167: 103 461 men and 74 706 women) without a known medical history or treatments that affect lipid metabolism. MAIN OUTCOME MEASURES: Dynamic trends in the above-mentioned lipid parameters with ageing were explored; turning points of age were established using age stratification and validated by fitted multivariate linear regression modelling. RESULTS: Age was found to be an independent factor extensively associated with lipid levels in both sexes when adjusted for serum glucose, body mass index, lifestyle, drinking and smoking. Age was positively associated with TC, logarithm-transformed TG (LnTG) and LDL-C levels in men ≤40, ≤40 and ≤60 years old (yo) and in women ≤60, ≤70 and ≤60 yo, respectively. Conversely, age correlated negatively with TC, LnTG and LDL-C levels in men ≥61, ≥41 and ≥61 yo and in women ≥61, ≥71 and ≥61 yo, respectively. TC, TG and LDL-C levels in women were initially lower than those in men but surpassed those in men in 51-55, 61-65 and 51-55 yo age groups. The trends in HDL-C levels with age were relatively irregular, although HDL-C levels in women were higher than in men for all age groups. CONCLUSIONS: The definition of dyslipidaemia, the atherosclerotic cardiovascular disease risk assessment and the initiation/goals of statin therapy should fully consider age-related trends in lipid levels and sex differences.

Identification of novel variants in MYO15A, OTOF, and RDX with hearing loss by next-generation sequencing.

BACKGROUND: Nonsyndromic hearing loss (NSHL) is the most common sensorineural disorder and one of the most common human defects. Autosomal recessive inheritance accounts for a huge percentage of familial cases. Next-generation sequencing (NGS) is a powerful molecular diagnostic strategy for NSHL. The combination of a microarray gene chip and NGS can better delineate the etiology and genetic cause of deafness in many cases. METHODS: One hundred and thirty-one unrelated students with NSHL who attend a special education school in Yunnan Province were recruited. Firstly, four common deafness-related genes (GJB2, GJB3, SLC26A4, and mtDNA 12S rRNA) were evaluated for mutations using a microarray kit. Furthermore, 227 known human deafness genes were sequenced to identify the responsible genetic variant of the proband in three Chinese families with autosomal recessive hearing loss. The mutational status of family members of the probands was validated by Sanger sequencing. RESULTS: Five novel variants were found in three families using NGS. In family 1, we identified compound heterozygosity at the MYO15A (OMIM, #600316), including an duplication variant c.3866dupC, p.His1290Alafs*25 and a 3-bp deletion (c.10251_10253del, p.Phe3420del), resulting in protein length changes and premature protein truncation, respectively. In family 2, two affected siblings from a consanguineous Chinese Dai family harbored an c.1274G>C, p.Arg425Pro missense variant in the OTOF (OMIM, #601071). In family 3, we identified compound heterozygosity for c.129_130del, p.His43Glnfs*28 and c.76_79del, p.Lys26* in the RDX gene (OMIM, #611022). CONCLUSION: Five novel variants were found in three families with NSHL. Our findings extend the mutational spectrum in deafness-related genes and will help physicians in better understanding the etiology of hearing loss.

Higher HbA1c and/or glucose levels alter the association patterns between glycated hemoglobin and fasting glucose levels.

AIMS: To verify the correlations between HbA1c and fasting glucose levels. METHODS: A cross-sectional study with 14,249 Chinese subjects. Objective was evaluated in pooled, age-stratified, HbA1c and fasting glucose-stratified populations. RESULTS: In pooled populations, the Pearson correlation coefficients (PCCs) of males and females were 0.684 (P < 0.001) and 0.800 (P < 0.001), respectively. HbA1c and fasting glucose maintained significant correlations within the group with HbA1c < 6.5% and glucose <7.0 mmol/L and the group with HbA1c ≥ 6.5% and glucose ≥7.0 mmol/L in both males (PCC: 0.342, P < 0.001; and PCC: 0.765, P < 0.001, respectively) and females (PCC: 0.318, P < 0.001 and PCC: 0.788, P < 0.001, respectively). The slopes increased from the group with HbA1c < 6.5% and glucose <7.0 mmol/L to the group with HbA1c ≥ 6.5% and glucose ≥7.0 mmol/L in both males (0.26-0.44) and females (0.31-0.46). Linear regression analysis showed that fasting glucose and age were two common factors positively associated with HbA1C, and red blood cell count and red cell distribution width were two common factors negatively associated with HbA1c in both males and females with HbA1c < 6.5% and glucose <7.0 mmol/L. The correlations changed dramatically in the groups with HbA1c ≥ 6.5% and glucose <7.0 mmol/L and HbA1c < 6.5% and glucose ≥7.0 mmol/L. CONCLUSIONS: High HbA1c and fasting glucose levels greatly altered the associations between HbA1c, glucose and age.

Differential analysis of disease risk assessment using binary logistic regression with different analysis strategies.

Objective To investigate the importance of controlling confounding factors during binary logistic regression analysis. Methods Male coronary heart disease (CHD) patients (n = 664) and healthy control subjects (n = 400) were enrolled. Fourteen indexes were collected: age, uric acid, cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B100, lipoprotein a, homocysteine, total bilirubin, direct bilirubin, indirect bilirubin, and γ-glutamyl transferase. Associations between these indexes and CHD were assessed by logistic regression, and results were compared by using different analysis strategies. Results 1) Without controlling for confounding factors, 14 indexes were directly inputted in the analysis process, and 11 indexes were finally retained. A model was obtained with conflicting results. 2) According to the application conditions for logistic regression analysis, all 14 indexes were weighed according to their variances and the results of correlation analysis. Seven indexes were finally included in the model. The model was verified by receiver operating characteristic curve, with an area under the curve of 0.927. Conclusions When binary logistic regression analysis is used to evaluate the complex relationships between risk factors and CHD, strict control of confounding factors can improve the reliability and validity of the analysis.

Combination of susceptibility gene and traditional risk factors might enhance the performance of coronary heart disease screening strategy.

Coronary heart disease (CHD) associated risk factors and susceptibility genes were studied in parallel for decades, however, the combination of the classic CHD risk factors and genetic risk factors has been rarely studied. Previously; we reported that a single nucleotide polymorphism (SNP) in the stromal cell-derived factor 1 (SDF-1) gene was associated with CHD risk; in addition, we also established a CHD screening strategy using traditional CHD risk factors as independent variables. To explore how to combine genetic factors and traditional risk factors in CHD screening strategy, the CHD probabilities were tested in 218 males and 121 females according to their stromal cell-derived factor 1 (SDF-1) genotypes using CHD screening equations we reported previously. The genotypes had not altered the distribution characteristics of age, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), lipoprotein(a) (LP(a)), homocysteine (HCY) and total bilirubin (TBil) in males and age, HDL-C, HCY and γ-glutamyl transpeptidase (GGT) in females among genotypes. However, the mean CHD probability of subjects with G/G genotype was significantly higher than that of subjects with A/A genotype (0.51 ± 0.35 vs. 0.31 ± 0.31, P = 0.035). The mean CHD probability of subjects with G homozygous and G heterozygote was 0.48 ± 0.34 which displayed a difference trend to that of subjects with A homozygous (0.31 ± 0.31, P = 0.059). Our data suggested that genetic risk factors might be used as a classification standard to improve current CHD screening strategies.

The associations between serum biomarkers and stenosis of the coronary arteries.

Serum biochemical indices reflect dynamic physiological and pathophysiological processes within the body, the associations between these markers and the number of stenotic coronary arteries have been rarely studied. 627 healthy controls and 1,049 coronary heart disease (CHD) patients were sequentially recruited in our hospital. The association patterns between serum biochemical markers and the numbers of stenotic coronary arteries were evaluated in a cross-sectional manner. Upon binary multiple logistic regression analysis, the risk factor patterns differed by gender. Age, high-density lipoprotein cholesterol (HDL) and homocysteine (HCY) were common risk factors for CHD in both males and females. Upon ordinal multiple logistic regression analysis, age, low-density lipoprotein cholesterol (LDL) and lipoprotein (Lp) (a) increased, and HDL decreased, as the number of stenotic coronary arteries increased in male patients. Age and Lp(a) were positively associated with the number of stenotic coronary arteries and total bilirubin (TBil) was negatively associated with the number of stenotic coronary arteries in female patients. Age and Lp(a) were common risk factors positively associated with the number of stenotic coronary arteries in both male and female patients. HDL and LDL were male-specific risk factors and TBil was a female-specific risk factor for an increasing number of stenotic coronary arteries. In conclusion, serum biomarker levels correlated with the number of stenotic coronary arteries and showed gender different patterns.

Screening for suspected coronary heart disease in patients, using integrated serum biochemical indices.

BACKGROUND: Many serum biochemical indices have been found to be associated with coronary heart disease (CHD); however, few studies have evaluated the value on screening CHD of the integrated serum biochemical indices. METHODS: In this study, 627 healthy controls and 1049 patients with CHD were recruited to develop CHD screening models for males and females using unconditional logistic regression. The performance of the screening models was evaluated by areas under the receiver operating characteristic (ROC) curves (AUCs), and externally validated in another population comprised of 190 healthy controls and 246 patients with CHD. RESULTS: Backward stepwise variable selection showed that increasing age, total cholesterol (TC), logarithm-transformed homocysteine (lnHCY), logarithm-transformed γ-glutamyl transpeptidase (lnGGT), and decreasing uric acid, logarithm-transformed triglyceride, apolipoprotein A (apoA) and apolipoprotein B (apoB), increased the detection of CHD in males. In comparison, increasing age, TC, lnHCY, lnGGT and high-density lipoprotein cholesterol versus low-density lipoprotein cholesterol, and decreasing apoA, apoB, logarithm transformed lipoprotein (A) and logarithm transformed total bilirubin, increased the detection of CHD in females. The AUCs for the screening models for males and females were 0.958 (95% CI 0.946 to 0.969) and 0.986 (95% CI 0.977 to 0.994), respectively. The performance of the screening models was further evaluated in external validation samples, the AUCs for males and females were 0.907 and 0.992, respectively. CONCLUSIONS: Our study suggests that integrated serum biochemical indices may be used to screen for suspected CHD in participants.

A single nucleotide polymorphism in the stromal cell-derived factor 1 gene is associated with coronary heart disease in Chinese patients.

Coronary heart disease (CHD) is highly prevalent globally and a major cause of mortality. Genetic predisposition is a non-modifiable risk factor associated with CHD. Eighty-four Chinese patients with CHD and 253 healthy Chinese controls without CHD were recruited. Major clinical data were collected, and a single nucleotide polymorphism (SNP) in the stromal cell-derived factor 1 (SDF-1) gene at position 801 (G to A, rs1801157) in the 3'-untranslated region was identified. The correlation between rs1801157 genotypes and CHD was evaluated by a multivariate logistic regression analysis. The allele frequency in the CHD and control groups was in Hardy-Weinberg equilibrium (HWE) (p>0.05). The frequency of the GG genotype in the CHD group (59.5%) was significantly higher than that in the control group (49.8%) (p=0.036). A number of variables, including male sex, age, presence of hypertension, and the levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), uric acid, and total bilirubin, were associated with CHD in a primary univariate analysis. In a multivariable logistic regression analysis, the GG genotype (GG:AA, odds ratio (OR)=2.31, 95% confidence interval (CI)=1.21-5.23), male sex, advanced age (≥60 years), presence of hypertension, LDL-C level≥3.33 mg/dL, HDL-C level<1.03 mg/dL, and TG level≥1.7 mg/dL were independent risk factors for CHD.

The GG genotype of telomerase reverse transcriptase at genetic locus rs2736100 is associated with human atherosclerosis risk in the Han Chinese population.

A single nucleotide polymorphism (SNP) in the second intron of human TERT (hTERT), rs2736100, acts as a critical factor in hTERT synthesis and activation. The rs2736100 SNP was found to be associated with susceptibility to many cancers. Recently, inhibition of telomerase and marked telomere shortening were determined to be closely associated with the increasing severity of atherosclerosis. The association between the SNP of rs2736100 and the presence of atherosclerosis was evaluated in 84 atherosclerosis patients and 257 healthy controls using multivariate logistic regression analyses. The proportion of the GG genotype in atherosclerosis patients (17.9%) was significantly higher than in the control group (9.7%). Eight variables, including age, gender, cholesterol, high density lipoprotein, homocysteine, total bilirubin, indirect bilirubin, and rs2736100 GG genotype, were associated with atherosclerosis with odds ratios of 1.88, 2.11, 1.66, 0.23, 1.27, 1.29, 1.53, and 1.74, respectively, using multivariate logistic regression analyses. Homozygous GG was demonstrated to be associated with the presence of atherosclerosis in our population.