Background-Recent studies on genome-wide association have identified common variants on chromosome 9p21 associated with coronary artery disease (CAD). Given that ischemic stroke and CAD share several aspects of etiology and pathogenesis, we investigated the association of variants on chromosome 9p21 with ischemic stroke and CAD in the Chinese Han population by capturing the majority of diversity in this locus using haplotype-tagging single-nucleotide polymorphisms. Methods and Results-We performed a shared control-cases study using 15 tagging single-nucleotide polymorphisms and 2 previously reported susceptibility single-nucleotide polymorphisms spanning 58 kb of the chromosome of 9p21 in a set of 558 patients with ischemic stroke, 510 patients with CAD, and 557 unaffected participants (controls) in the Chinese Han population. The association analyses were performed at both SNP and haplotype levels. We further verified our findings in an independent cohort of 442 ischemic stroke cases and 502 control subjects. In the first study, rs2383206, rs1004638, and rs10757278 in block 3 were significantly associated with CAD but not with ischemic stroke independent of traditional cardiovascular risk factors in additive model (Pϭ0.002 to 0.0001, qϭ0.026 to 0.004).Analysis from all blocks revealed that haplotype profiles of block 3 on 9p21 were significantly different between shared control and cases of CAD (Pϭ1.3ϫ10 Ϫ10 , qϭ1.2ϫ10 Ϫ9 ) and ischemic stroke (Pϭ1.7ϫ10 Ϫ6 , qϭ7.7ϫ10 Ϫ6). In the expanded second case-control study, block 3 on 9p21 remained associated with ischemic stroke (Pϭ2.6ϫ10 Ϫ4 , qϭ6.3ϫ10 Ϫ4 ). Conclusions-Our results suggest for the first time that 9p21 is a shared susceptibility locus, strongly for CAD and weakly for ischemic stroke, in a Chinese Han population. (Circ Cardiovasc Genet. 2009;2:338-346.)Key Words: cerebrovascular disorders Ⅲ coronary disease Ⅲ genetics Ⅲ ischemic stroke Ⅲ 9p21 Ⅲ single-nucleotide polymorphisms Ⅲ haplotypes Ⅲ Chinese Han population C oronary artery disease (CAD) and stroke are the leading causes of morbidity and mortality worldwide. 1 In China, more than 2.5 million people are affected by stroke and 1 million are affected by heart attack, leading to more than 2 million deaths each year (http://www.moh.gov.cn). It was found that the conventional cardiovascular risk factors such as abnormal lipid metabolism, smoking, diabetes, and hypertension only account for 50% to 60% of the disease susceptibility, 2,3 indicating that other risk factors such as genetic predisposition are also implicated in the pathogenesis of disease development. Indeed, over the last decade, numerous genetic variations have been reported to be associated with CAD and ischemic stroke. 4 -6 Particularly, a genomic region on chromosome 9p21 was found to be consistently associated with CAD in several populations of European origin and East Asian origin, 7-13 although genetic heterogeneity was observed in blacks. 9,14 Clinical Perspective on p 346Given the fact that ischemic stroke and CAD share several aspec...

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20-Hydroxyeicosatetraenoic acid (20-HETE) has been shown to play an important role in cerebral vascular function. We hypothesized that polymorphisms in genes encoding 20-HETE synthesizing enzymes might confer susceptibility to stroke. To test the hypothesis, haplotype tagging SNPs (htSNPs) and potential functional polymorphisms of CYP4A11 and CYP4F2 genes were genotyped in 558 ischemic stroke patients, 221 hemorrhagic stroke patients and 557 controls. The association analyses were performed at both SNP and haplotype levels. We further verified our findings in an independent cohort of 551 ischemic stroke cases and 48 hemorrhagic stroke subjects and 694 unaffected controls. We identified CYP4A11 C-296T and CYP4F2 V433M were associated with significantly increased risk of ischemic stroke (CT+TT vs CC, adjusted odds ratio (OR) 1.50, 95% confidence interval (CI) 1.17–1.93, Pcombined=0.001, Pcorr=0.008; V/M+M/M vs. V/V, OR 1.38, 95% CI, 1.15–1.65, Pcombined=5.6×10−4, Pcorr=0.005, respectively) Interestingly, the effects of CYP4F2 V433M on ischemic stroke in our study was only evident in male subjects. Our results suggest that genetic variation in CYP4A11 and CYP4F2 alters susceptibility to stroke in the Han Chinese population.

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Refractory nephrotic syndrome (RNS) is an immune-related kidney disease with poor clinical outcomes. Standard treatments include corticosteroids as the initial therapy and other immunosuppressants as second-line options. A substantial proportion of patients with RNS are resistant to or dependent on immunosuppressive drugs and often experience unremitting edema and proteinuria, cycles of remission and relapse, and/or serious adverse events due to long-term immunosuppression. Traditional Chinese medicine has a long history of treating complicated kidney diseases and holds great potential for providing effective treatments for RNS. This review describes the Chinese medical theories relating to the pathogenesis of RNS and discusses the strategies and treatment options using Chinese herbal medicine. Available preclinical and clinical evidence strongly supports the integration of traditional Chinese medicine and Western medicine for improving the outcome of RNS. Herbal medicine such as Astragalus membranaceus, Stephania tetrandra S. Moore, and Tripterygium wilfordii Hook F can serve as the alternative therapy when patients fail to respond to immunosuppression or as the complementary therapy to improve therapeutic efficacy and reduce side effects of immunosuppressive agents. Wuzhi capsules (Schisandra sphenanthera extract) with tacrolimus and tetrandrine with corticosteroids are two herb-drug combinations that have shown great promise and warrant further studies.

BackgroundSmall dense low density lipoprotein-cholesterol (sdLDL-C), cholesterol ratios and carotid-femoral pulse wave velocity (cf-PWV) impart risk for all-cause morbidity and mortality independently of conventional cardiovascular disease (CVD) risk factors. This study was designed to identify feasible indicators for predicting arterial stiffness progression.MethodsWe followed up 816 normotensive participants without diabetes or CVD for nearly 5.0 years. Cholesterol parameters, ratios and other clinical and laboratory data were collected at baseline. cf-PWV were measured at baseline and the end of follow-up.ResultsPWV progression subjects had higher levels of PWV parameters, sdLDL-C and TG/HDL-C ratio. sdLDL-C and TG/HDL-C were significantly correlated with all PWV parameters. Multiple regression models showed that sdLDL-C was closely associated with follow-up PWV (β = 0.222, p < 0.001) and △PWV (β = 0.275, p < 0.001). TG/HDL-C was only one cholesterol ratios that associated with all PWV parameters. sdLDL-C (OR = 2.070, 95%CI: 1.162 to 3.688, p = 0.014) and TG/HDL-C (OR = 1.355, 95%CI: 1.136 to 1.617, p = 0.001) could significantly determine the progression of PWV after correction for covariates. High sd-LDL-C quantiles subjects were more likely to develop arterial stiffness progression than low quantiles (Tertiles 3 vs Tertiles1, RR = 2.867, 95%CI: 1.106 to 7.434, p = 0.03).ConclusionWe founded that sdLDL-C and TG/HDL-C ratio can independently predict arterial stiffness progression in normotensive subjects, and high level sdLDL-C and TG/HDL-C ratio were associated with a higher risk of arterial stiffness.