Angiotensin-converting enzyme (ACE) inhibition in type 2, diabetic patients – interaction with ACE insertion/deletion polymorphism

Angiotensin-converting enzyme (ACE) insertion(I)/deletion (D) polymorphism may modify the effect of inhibition of the renin–angiotensin–aldosterone system (RAAS) on survival and cardiorenal outcomes in type 2, diabetes. A consecutive cohort of 2089 Chinese type 2 diabetic patients with mean (±standard deviation) age of 59.7±13.1 years were genotyped for this polymorphism by polymerase chain reaction method and were followed prospectively for a median period of 44.6 (interquartile range: 23.7, 57.5) months. Clinical outcomes, including all-cause mortality, cardiovascular and renal end points, were examined. The frequency for I allele was 67.1 and 32.9% for D allele, with observed genotype frequencies of 45.8, 42.6, and 11.6% for 3, DI and DD, respectively. ACE DD polymorphism was an independent predictor for renal end point with hazard ratio (HR) (95% confidence interval) of 1.72 (1.16, 2.56), but not for cardiovascular end point or mortality. After controlling for confounding factors, including ACE I/D genotype, the usage of RAAS inhibitors was associated with reduced risk of mortality (HR 0.34 (0.23, 0.50)) and renal end point (HR 0.55 (0.40, 0.75)). On subgroup analysis, the beneficial effects on survival (II vs DI vs DD: HR 0.29 (0.16, 0.51) vs 0.25 (0.14, 0.46) vs 1.33 (0.41, 4.31)) and renoprotection (II vs DI vs DD: 0.52 (0.30, 0.90) vs 0.43 (0.25, 0.72) vs 0.95 (0.43, 2.12)) were most evident in II and DI carriers. In conclusion, inhibition of RAAS was associated with reduced risk of mortality and occurrence of renal end point in Chinese type 2 diabetic patients. These benefits were most evident among II and DI carriers

Asthma and atopy are associated with chromosome 17q21 markers in Chinese children

Background: Single‐nucleotide polymorphism (SNP)‐based genome‐wide association study revealed that markers on chromosome 17q21 were linked to childhood asthma but not atopy in Caucasians, with the strongest signal being detected for the SNP rs7216389 in the gene. Such association was unknown in Chinese. This study delineated the allele and genotype frequencies of 10 SNPs at chromosome 17q21, and investigated the relationship between these SNPs and asthma and plasma IgE in southern Chinese children. Methods: Asthmatic children and non‐allergic controls were recruited from pediatric clinics. Their plasma total and aeroallergen‐specific IgE concentrations were measured by immunoassay. Ten SNPs on 17q21 region were genotyped by multiplex SNaPshot™, and their genotype associations with asthma traits analyzed using multivariate regression. Results: 315 patients and 192 controls were enrolled. The allele frequency for C allele of rs7216389 varied significantly from 0.232 in our controls, 0.389 in Han Chinese to 0.536 in Caucasians. Asthma diagnosis was associated with rs11650680 and five other SNPs including rs7216389 (=0.019–0.034), whereas atopy was associated only with rs11650680 (=0.0004). Linear regression revealed the covariates for plasma total IgE to be significant for rs11650680 (=0.008–0.0002). Haplotypic associations were found with atopy and increased plasma total IgE, with the respective odds ratios and 95% confidence intervals for TTTCCGTT haplotype to be 0.21 and 0.09–0.52 (=0.0002) and 0.41 and 0.18–0.90 (=0.025). Conclusion: Childhood asthma and atopy are associated with chromosome 17q21 in Chinese, but such association may involve genes other than in this region

Association between candidate genes and spirometric variables in Chinese

Background: Asthma is caused by complex interactions between multiple susceptibility genes and environmental factors. Three genes (ARG1, ADRB2 and CRHR2) were reported to be associated with bronchodilator response in Caucasians, whereas NOS1 and NOS3 were important components of the arginase 1 pathway. GSDM1 and TOP2A, located on chromosome 17q21 as a reproducible locus identified by asthma genome-wide association study in other ethnic groups, were also candidate genes for asthma and atopy in our Chinese children. This study investigated the associations between spirometric variables and single-nucleotide polymorphisms (SNPs) of these seven candidate genes. Methods: This study recruited both children (312 cases and 70 controls; aged 6-17 years) and adults (345 cases and 652 controls; aged ≥ 18 years). Spirometry was performed before and 30 minutes following salbutamol inhalation. Their forced expiratory volume in 1-second (FEV1) and forced vital capacity (FVC) were then measured. Thirteen SNPs of ARG1, ADRB2, CRHR2, NOS1, NOS3, GSDM1 and TOP2A were genotyped by TaqMan SNP genotyping assays using ABI Prism 7900HT thermocycler, and their associations with spirometric variables in our subjects were analyzed by multivariate linear regression. Results: All SNPs followed Hardy-Weinberg equilibrium. In our adults, the minor allele of rs3756780 on ARG1 was associated with an additive protective effect against asthma (odds ratio 0.71, 95% confidence interval 0.54-0.93; P=0.013). Multivariate linear regression revealed FEV1 to be associated with SNPs of ARG1, CRHR2, GSDM1 and TOP2A (P=0.002-0.044), whereas FEV1/FVC was associated with SNPs of ARG1 and TOP2A (P=0.021-0.050). No significant association was found between spirometric variables and ADRB2. Among our children, FEV1 reversibility was associated with rs1003929 of CRHR2 and rs1007654 of GSDM1 (P=0.014 and 0.004, respectively). Conclusions: This study identifies discrepant genetic associations for spirometric parameters between Chinese adults and children. Both CRHR2 and GSDM1 are associated with FEV1 in adults and FEV1 reversibility in children, whereas ARG1 and TOP2A are associated with FEV1 and FEV1/FVC only in adults. These findings highlight the importance of these candidate genes in modulating airflow limitation. None of ADRB2, NOS1 or NOS3 is a major gene for spirometric variables in the Chinese population

The Asian project for collaborative derivation of reference intervals: (1) strategy and major results of standardized analytes

Background : A multicenter study conducted in Southeast Asia to derive reference intervals (RIs) for 72 commonly measured analytes (general chemistry, inflammatory markers, hormones, etc.) featured centralized measurement to clearly detect regionality in test results. The results of 31 standardized analytes are reported, with the remaining analytes presented in the next report. Method : The study included 63 clinical laboratories from South Korea, China, Vietnam, Malaysia, Indonesia, and seven areas in Japan. A total of 3541 healthy individuals aged 20 \u2013 65 years (Japan 2082, others 1459) were recruited mostly from hospital workers using a well-defined common protocol. All serum specimens were transported to Tokyo at 12 80 \ub0 C and collectively measured using reagents from four manufacturers. Three-level nested ANOVA was used to quantitate variation (SD) of test results due to region, sex, and age. A ratio of SD for a given factor over residual SD (representing net between-individual variations) (SDR) exceeding 0.3 was considered significant. Traceability of RIs was ensured by recalibration using value-assigned reference materials. RIs were derived parametrically. Results : SDRs for sex and age were significant for 19 and 16 analytes, respectively. Regional difference was significant for 11 analytes, including high density lipoprotein (HDL)-cholesterol and inflammatory markers. However, when the data were limited to those from Japan, regionality was not observed in any of the analytes. Accordingly, RIs were derived with or without partition by sex and region. Conclusions : RIs applicable to a wide area in Asia were established for the majority of analytes with traceability to reference measuring systems, whereas regional partitioning was required for RIs of the other analytes