Development and evaluation of a candidate reference measurement procedure for detecting 17α-hydroxyprogesterone in dried blood spots using isotope dilution liquid chromatography tandem mass spectrometry.

17α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is challenging due to its low physiological concentration. The high false-positive rates of immunoassays necessitate the development of more accurate methods. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers increased specificity and sensitivity, yet standardized procedures for 17α-OHP measurement are required for clinical application. A candidate reference measurement procedure (cRMP) using isotope dilution LC-MS/MS was developed for 17α-OHP quantification in DBS. By utilizing stable isotope-labeled D8-17α-OHP as an internal standard, the cRMP was optimized, covering sample preparation, calibration, and LC-MS/MS analysis. The method performance was validated across several parameters, including precision, accuracy, specificity, detection limits, and matrix effects. Clinical applicability was further assessed through the establishment of reference intervals for healthy newborns. The developed cRMP exhibited a linear range of 1.00 to 80.00 ng/mL for 17α-OHP, with detection and quantification limits of 0.14 ng/mL and 0.52 ng/mL, respectively. Inter- and intraday precision demonstrated coefficients of variation within 1.27 to 5.69%. The recovery rates and matrix effects were well within acceptable limits, ensuring method reliability. Clinical application showed distinct reference intervals for healthy newborns that were unaffected by sex but influenced by weight and gestational age. This method significantly enhances CAH diagnostic accuracy in newborns, providing a valuable tool for clinical laboratories and improving newborn screening program standardization and traceability.

Rapid and multi-target genotyping of Helicobacter pylori with digital microfluidics.

Helicobacter pylori (H. pylori) infection correlates closely with gastric diseases such as gastritis, ulcers, and cancer, influencing more than half of the world's population. Establishing a rapid, precise, and automated platform for H. pylori diagnosis is an urgent clinical need and would significantly benefit therapeutic intervention. Recombinase polymerase amplification (RPA)-CRISPR recently emerged as a promising molecular diagnostic assay due to its rapid detection capability, high specificity, and mild reaction conditions. In this work, we adapted the RPA-CRISPR assay on a digital microfluidics (DMF) system for automated H. pylori detection and genotyping. The system can achieve multi-target parallel detection of H. pylori nucleotide conservative genes (ureB) and virulence genes (cagA and vacA) across different samples within 30 min, exhibiting a detection limit of 10 copies/rxn and no false positives. We further conducted tests on 80 clinical saliva samples and compared the results with those derived from real-time quantitative polymerase chain reaction, demonstrating 100% diagnostic sensitivity and specificity for the RPA-CRISPR/DMF method. By automating the assay process on a single chip, the DMF system can significantly reduce the usage of reagents and samples, minimize the cross-contamination effect, and shorten the reaction time, with the additional benefit of losing the chance of experiment failure/inconsistency due to manual operations. The DMF system together with the RPA-CRISPR assay can be used for early detection and genotyping of H. pylori with high sensitivity and specificity, and has the potential to become a universal molecular diagnostic platform.

2023 China Guidelines for Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

2023 Chinese guideline for lipid management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "Chinese guideline for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Familial hypercholesterolaemia (FH) is a common hereditary genetic disorder, characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] concentrations, leading to atherosclerotic cardiovascular disease (ASCVD). Two types of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors- alirocumab and evolocumab- are efficient drugs in the treatment of FH, which can effectively reduce Lp(a) levels. MATERIAL AND METHODS: Embase, MEDLINE, and PubMed up to November 2022 were searched for randomized clinical trials (RCTs) evaluating the effect of alirocumab/evolocumab and placebo treatment on plasma Lp(a) levels in FH. Statistics were analysed by Review Manager (RevMan 5.3) and Stata 15.1. RESULTS: Eleven RCTs involved a total of 2408 participants. Alirocumab/evolocumab showed a significant efficacy in reducing Lp(a) [weighted mean difference (WMD): -20.10%, 95% confidence interval (CI): -25.59% to -14.61%] compared with placebo. In the drug type subgroup analyses, although the efficacy of evolocumab was slightly low (WMD: -19.98%, 95% CI: -25.23% to -14.73%), there was no difference with alirocumab (WMD: -20.54%, 95% CI: -30.07% to -11.02%). In the treatment duration subgroup analyses, the efficacy of the 12-week duration group (WMD: -17.61%, 95% CI: -23.84% to -11.38%) was lower than in the group of ≥ 24 weeks' duration (WMD: -22.81%, 95% CI: -31.56% to -14.07%). In the participants' characteristics subgroup analyses, the results showed that no differential effect of alirocumab/evolocumab therapy on plasma Lp(a) concentrations was observed (heterozygous FH [HeFH] WMD: -20.07%, 95% CI: -26.07% to -14.08%; homozygous FH [HoFH] WMD: -20.04%, 95% CI: -36.31% to -3.77%). Evaluation of all-cause adverse events (AEs) between alirocumab/evolocumab groups and placebo groups [relative risk (RR): 1.05, 95% CI: 0.98-1.12] implied no obvious difference between the 2 groups. CONCLUSIONS: Anti-PCSK9 drugs (alirocumab and evolocumab) may be effective as therapy for reducing serum Lp(a) levels in FH, and no differences were observed in treatment durations, participant characteristics, and other aspects of the 2 types of PCSk9 inhibitors. However, further experimental studies and RCTs are warranted to clarify the mechanism of PSCK9 inhibitors to lowering Lp(a) concentrations in FH.

Lactate dehydrogenase and aspartate aminotransferase levels associated with the severity of COVID­19: A systematic review and meta­analysis.

Lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) are important indicators of cardiovascular, muscle and liver lesions, and can be used as prognostic indicators for infectious diseases, such as coronavirus disease 2019 (COVID-19). The present systematic review and meta-analysis assessed the prognostic value of LDH and AST levels for COVID-19 severity. Ovid-Medline, PubMed, Embase and The Cochrane Library were used to search for articles, according to the inclusion and exclusion criteria, until July 2022. The meta-analysis was performed using Revman5.3 and Stata15.1. Standardized mean difference (SMD) and 95% confidence intervals (CIs) of LDH and AST concentrations were analyzed using a random-effects model. Heterogeneity was investigated using meta-regression and subgroup methods. A total of 4,342 patients with COVID-19 in 23 articles were included in the present study. LDH (SMD=1.21; 95% CI: 0.98, 1.44) and AST (SMD=0.68; 95% CI: 0.54, 0.81) were significantly higher in patients with severe COVID-19 compared with in those with non-severe COVID-19. Serum LDH and AST levels in critically ill patients with COVID-19 were increased, suggesting a correlation between the levels of LDH and AST and the severity of COVID-19. These findings may help to develop a risk-stratified approach to the care of patients with this disease.

Genetic analysis of a large Han Chinese family line with schizoaffective psychosis.

To locate the specific susceptibility genes of a high incidence of schizoaffective disease (SAD) with autonomic dominant inheritance, we recruited a family group from Henan Province with a high incidence of SAD, including 19 individuals sampled from five generations. We used a genome-wide high-density SNP chip to perform genotype detection. The LINKAGE package and MENDEL programs were used for. The two-point and multipoint analyses were calculated by Merlin and SimWalk2 software to obtain the nonparametric linkage (NPL) value, corresponding P value, and parameter linkage limit of detection (LOD) value. Genome-wide linkage analysis yielded a significant linkage signal located on the short arm of chromosome 19. In the dominant genetic model, the LOD of the multipoint parametric analysis was 2.5, and the nonparametric analysis was 19.4 (P < 0.00001). Further haploid genotype analysis localized the candidate region in the 19p13.3-13.2 region, beginning at rs178414 and ending at rs11668751 with a physical length of approximately 4.9 Mb. We believe that the genes responsible for SAD are in this region.

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world, multi-center, cohort study.

BACKGROUND: There is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia. OBJECTIVE: To define the characteristics of phenotypic and genetic HoFH probands from mainland China. METHODS: We collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test. RESULTS: A total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH. CONCLUSIONS: This report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.

Discordant risk: overweight and cardiometabolic risk in Chinese adults.

OBJECTIVE: Recent US work identified "metabolically healthy overweight" and "metabolically at risk normal weight" individuals. Less is known for modernizing countries with recent increased obesity. DESIGN AND METHODS: Fasting blood samples, anthropometry and blood pressure from 8,233 adults aged 18-98 in the 2009 nationwide China Health and Nutrition Survey, were used to determine prevalence of overweight (Asian cut point, BMI ≥ 23 kg/m(2) ) and five risk factors (prediabetes/diabetes (hemoglobin A1c ≥ 5.7%) inflammation (high-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/l), prehypertension/hypertension (Systolic blood pressure/diastolic blood pressure ≥ 130/85 mm Hg), high triglycerides (≥ 150 mg/dl), low high-density lipoprotein cholesterol (<40 (men)/ <50 mg/dl (women)). Sex-stratified, logistic, and multinomial logistic regression models estimated concurrent obesity and cardiometabolic risk, with and without abdominal obesity, adjusting for age, smoking, alcohol consumption, physical activity, urbanicity, and income. RESULTS: Irrespective of urbanicity, 78.3% of the sample had ≥ 1 elevated cardiometabolic risk factor (normal weight: 33.2% had ≥ 1 elevated risk factor; overweight: 5.7% had none). At the age of 18-30 years, 47.4% had no elevated risk factors, which dropped to 6% by the age 70, largely due to age-related increase in hypertension risk (18-30 years: 11%; >70 years: 73%). Abdominal obesity was highly predictive of metabolic risk, irrespective of overweight (e.g., "metabolically at risk overweight" relative to "metabolically healthy normal weight" (men: relative risk ratio (RRR) = 39.06; 95% confidence interval (CI): 23.47, 65.00; women: RRR = 22.26; 95% CI: 17.49, 28.33)). CONCLUSION: A large proportion of Chinese adults have metabolic abnormalities. High hypertension risk with age, underlies the low prevalence of metabolically healthy overweight. Screening for cardiometabolic-related outcomes dependent upon overweight will likely miss a large portion of the Chinese at risk population.

[Short-term impact of modified blood-lipid reports on physicians' lipid lowering drug prescribing behavior and knowledge improvement on dyslipidemia].

OBJECTIVE: To compare the physicians' lipid lowering drug prescribing behavior and knowledge on dyslipidemia before and at 8 months after new-issued blood-lipid reports in our hospital. METHOD: Blood-lipid reports in our hospital is newly modified in that the classification of dyslipidemia and lipid-lowering guideline and target lipid level are listed on the back of lipid report besides the normal lipid value listed immediately after the measured lipid levels. Physicians' lipid lowering drug prescribing behavior and knowledge on dyslipidemia before and at 8 months after new-issued blood-lipid reports were examined in 143 doctors from various departments before and at 8 months after new-issued lipid reports. RESULTS: At 8 months after the new issued lipid reports, doctors' cognition rate about the guideline was significantly increased [83.9% (120/143) vs. 67.1% (96/143), P < 0.001] and the guideline was considered more helpful on daily practice [75.3% (58/77) vs. 55.8% (43/77), P = 0.005] compared to baseline. However, the prescription rate of dyslipidemia therapy did not change significantly (69.2% vs. 63.2%, P = 0.117) at 8 months after the new issued lipid reports. CONCLUSIONS: The modification of the blood-lipid reports improved doctors' knowledge on dyslipidemia and on the "Chinese guidelines on prevention and treatment of dyslipidemia in adults". However, the lipid lowering drug prescribing behavior remained unchanged at 8 months after the modification of the lipid reports. Further investigation is warranted to see if the lipid lowering drug prescribing behavior could be changed in the long-term.

Oxidative stress and diabetes mellitus.

Increasing evidences have suggested that oxidative stress plays a major role in the pathogenesis of diabetes mellitus (DM). Oxidative stress also appears to be the pathogenic factor in underlying diabetic complications. Reactive oxygen species (ROS) are generated by environmental factors, such as ionizing radiation and chemical carcinogens, and also by endogenous processes, including energy metabolism in mitochondria. ROS produced either endogenously or exogenously can attack lipids, proteins and nucleic acids simultaneously in living cells. There are many potential mechanisms whereby excess glucose metabolites traveling along these pathways might promote the development of DM complication and cause pancreatic ß cell damage. However, all these pathways have in common the formation of ROS, that, in excess and over time, causes chronic oxidative stress, which in turn causes defective insulin gene expression and insulin secretion as well as increased apoptosis. Various methods for determining biomarkers of cellular oxidative stress have been developed, and some have been proposed for sensitive assessment of antioxidant defense and oxidative damage in diabetes and its complications. However, their clinical utility is limited by less than optimal standardization techniques and the lack of sufficient large-sized, multi-marker prospective trials.

[Usability of the laboratory report and knowledge of lipid-lowering in out-patients from dyslipidemia-related departments].

OBJECTIVE: To investigate the usability of laboratory test report from the angle of patients and understand to what degree the patients master the knowledge of lipid-lowering. METHODS: A total of 508 outpatients, selected from a Grade III-A general hospital, were queried by a questionnaire, their medical records and test reports were reviewed and their heights and weights were measured. In the study, 431 of them fulfilled the inclusion criteria and their information about lipid lowering treatment and treatment compliance were collected. RESULTS: Of the 508 subjects, 90.2% (458/508) read the report seriously; however, only 47.4% (240/508) took drugs according to the doctor's prescription even if the tests were "normal". Of the 431 lipid-lowering therapy related patients, only 26.4% (112/431) chose right in their cardiovascular risk classification, and less than 37.1% (160/431) agreed that "different people had different lipid lowering target". Of the 381 patients who needed the lipid-lowering treatment, 71.7% (273/381) recognized the need for treatment, but 98.7% (376/381) answered a wrong target for treatment; 60.9% (232/381) recognized that the reference values given in the laboratory test reports should be the target for treatment. Of the 246 patients under the lipid-lowering treatment, 35.4% (87/246)had reached their treatment goals, and only 52.0% (128/246) had a good compliance. CONCLUSION: Most patients read and trusted the laboratory test reports. However, dyslipidemia patients scarcely knew their lipid lowering treatment goals and their cardiovascular risk levels. The compliance of patients was poor, and the goal attainment was low. The laboratory medicine department should find out a simple and intuitional way to change the current situation.

Investigation of the relationship between apolipoprotein E gene polymorphisms and hepatitis B virus infection in northern China.

BACKGROUND: Certain genetic polymorphisms can lead to differences in immunity function, resulting in different clinical outcomes for hepatitis B virus (HBV) patients. The aim of this study was to investigate the association between apolipoprotein E (ApoE) gene polymorphisms and HBV infection status in northern Chinese individuals. METHODS: Genomic DNA was extracted using an improved sodium iodide (NaI) method from the peripheral blood of 270 patients with hepatitis B and 112 healthy controls. Multiplex Amplification Refractory Mutation System (Multi-ARMS) was performed to analyze ApoE gene polymorphisms with three alleles (ɛ2, ɛ3, ɛ4) in patients and controls. A chemiluminescence assay was used to detect serological markers for hepatitis B infection status. RESULTS: An improved PCR system for the detection of ApoE gene polymorphisms was established successfully. The frequency of the ɛ2 allele in patients with HBV infection was higher than that of normal controls (p<0.05). The ɛ2 allele, compared with the ɛ3 and ɛ4 alleles, showed positive correlation with the different HBV infection models [odds ratio (OR)=1.735, 95% confidence interval (CI): 1.509-1.999, p<0.01; OR=1.768, 95% CI: 1.554-2.011, p<0.01]. The OR for the ApoE ɛ2 allele was 1.503 in a multivariate unconditional logistic regression model (OR=1.503, 95% CI: 1.212-1.754, p<0.01). CONCLUSIONS: Our results indicated that the ApoE gene polymorphism was associated with HBV infection, and the ɛ2 allele showed positive correlation with HBV infection in northern China.

[Levels of homocysteine and polymorphisms of homocysteine metabolism-related enzymes in patients with type 2 diabetes mellitus and coronary heart disease].

OBJECTIVE: To explore the significance of Hey, the gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677 T and cystathionine beta- synthase (CBS844) ins68 in type 2 diabetes mellitus (DM) with coronary heart disease (CHD) in China. Methods We selected 70 patients with type 2 DM and CHD, 71 type 2 diabetes patients, and 85 controls in Han nationality from northern China. Hey levels were measured by fluorescence polarization immunoassay (FPIA) and the plasma folate and vitamin B12 levels by microparticle enzyme immunoassay (MEIA). The gene polymorphisms of the MTHFR C677 T were determined by PCR- RFLP assay and the gene polymorphisms of the CBS 844ins68 were determined by PCR assay. RESULTS: The plasma Hey levels in DM with CHD group (14.8 micromol/L) were significantly higher than in DM group (11.1 micromol/L) and control group (11.2 micromol/L), (P < 0.01). The levels of plasma folate and Vitamin B12 in DM with CHD group were significantly lower than in DM group and control group, (P < 0.05). The T allelic frequency of MTHFR in DM and CHD group was significantly higher than that in DM group and controls (45% vs 26.8%, 31.2%, P < 0.01). There were no significant differences in the frequencies of CBS 844ins68 polymorphism among 3 groups (P > 0.05). Logistic-regression analysis indicated that the OR of HHcy was 4.547 (95% CI 1.97-10.496) (P < 0.01), the OR of MTHFR 677 with T (including MTHFR CT genotype and Tr genotype)was 2.369 (95% CI 1.160-4.841), (P = 0.018), and the OR of CBS 844ins68 was 0.384 (95% CI 0.033-4.423), (P = 0.443). CONCLUSION: Hyperhomocysteinemia and MTHFR with T allele might be the risk factors for DM with CHD in northern Chinese Han population.

Effects of hydrogen sulfide on homocysteine-induced oxidative stress in vascular smooth muscle cells.

Hydrogen sulfide (H(2)S) is an important gasotransmitter that generated in mammalian cells from l-cysteine metabolism. Little is known about its protective role in oxidative stress. In the present study, we investigated whether H(2)S could affect homocysteine (HCY)-induced cytotoxicity and oxidative stress in vascular smooth muscle cells. Cultured A-10 cells were exposed to HCY treatment in the presence or absence of NaHS (donor of H(2)S). HCY induced cytotoxicity, increased levels of H(2)O(2), ONOO(-), and O2- in a time- and concentration-dependent manner. Low levels of NaHS (30 or 50microM) protected A-10 cells from cytotoxicity, decreased the production of H(2)O(2), ONOO(-), and O2- in the presence of HCY. Furthermore, NaHS enhanced inhibitory effects of NAC, GSH, DPI, SOD, L-NAME, or vitamin C on oxidized DCF or O2- formation induced by HCY. In conclusion, our findings provide the first evidence that low levels of H(2)S decrease reactive oxygen species and improve cell viability and by doing so limit cellular damage induced by HCY.

Apolipoprotein B gene 3'VNTR polymorphism: association with plasma lipids and coronary heart disease in Han Chinese.

BACKGROUND: Studies that considered polymorphisms within the apolipoprotein B (APOB) gene as risk factors for coronary heart disease (CHD) have reported conflicting results. METHODS: The phenotypic effects of the 3'VNTR polymorphism of the APOB gene on the susceptibility to CHD were investigated in 120 unrelated healthy individuals and 137 CHD patients. The internal structure of APOB gene 3'VNTR alleles was also analyzed by the methods of SspI restriction mapping and DNA sequencing of the allele fragments. RESULTS: In total, 14 segregating alleles and 32 genotypes of APOB gene 3'VNTR were characterized in the pooled total of 257 subjects. The frequency of 3'VNTR-B alleles [hypervariable element (HVE) > or =38)] in the CHD cases was higher than that of the controls (10.95% vs. 5.00%, p<0.05). 3'VNTR-B allele was dependently related to total cholesterol levels (p<0.05). Compared with SS homozygotes, 3'VNTR-B allele carriers were associated with an increased risk of CHD (OR=2.137, 95% CI=1.055-4.328, p=0.0349). No significant differences in the internal structure and sequences of APOB gene 3'VNTR alleles were found between cases and controls. CONCLUSIONS: APOB gene 3'VNTR polymorphism exerts an impact on lipid metabolism and may contribute to the susceptibility to the development of CHD in Han Chinese.

Apolipoprotein A5 gene polymorphism -1131T-->C: association with plasma lipids and type 2 diabetes mellitus with coronary heart disease in Chinese.

Type 2 diabetes mellitus (DM) is associated with significant abnormalities of lipoprotein metabolism and coronary heart disease (CHD). The most commonly recognized lipid abnormality in type 2 DM is hypertriglyceridemia, which is known to be an independent risk factor for CHD in diabetics. The -1131T-->C polymorphism found in the newly identified apolipoprotein A5 ( APOA5 ) gene has been found to be associated with elevated plasma triglyceride (TG) concentrations in different racial groups. In this study, DNA samples from 155 control subjects, 172 type 2 diabetics and 113 type 2 DM patients with CHD were analyzed to examine the influence of APOA5 1131T-->C polymorphism on plasma lipids and the susceptibility to CHD in type 2 diabetics. The frequency of the APOA5 -1131C allele in the DM+CHD group was significantly higher than that of control subjects (37.2% vs. 27.7%, p=0.021). The distribution of the APOA5 -1131T-->C genotypes (TT, TC and CC) was 36.3%, 53.1% and 10.6% in type 2 DM patients with CHD, and 53.6%, 37.4% and 9.0% in controls, respectively (p=0.018). The frequencies of alleles and genotypes in type 2 diabetics were not significant compared to controls. In controls, plasma TG concentrations in subjects with the TT genotype were significantly lower than in those with TC/CC (0.92, 1.28 and 1.35 mmol/L for TT, TC and CC, respectively; p = 0.003 by ANOVA). These data suggest that the APOA5 -1131T-->C polymorphism might play a role in elevated plasma TG levels in type 2 diabetic patients in the Chinese population.