中国汉族人群中RELN基因rs7341475位点与精神分裂症的相关性分析

精神分裂症是一种常见的复杂精神疾病.大量的实验证据表明,遗传因素在精神分裂症的发生中起到了重要的作用.截至目前,有报道称至少100个基因与精神分裂症相关,但它们在不同人群中的重复性不好.在这些基因中,RELN在多个人群中都被证实与精神分裂症相关,表明它可能是一个真实的易感基因.目前,在RELN基因上有很多个单核苷酸多态性位点被证实与精神分裂症相关,其中研究最多的是通过全基因组关联分析发现的在RELN基因第四个内含子中的单核苷酸多态性位点rs7341475,它被证明与精神分裂症的发生相关.为了验证该位点在中国人群中是否与精神分裂症相关,作者对来自中国玉溪的病例——对照样本(400位患者和400位正常人)进行了遗传分析.结果显示,在该样本中rs7341475与精神分裂症不相关,这表明rs7341475在中国人群中可能不是致病多态性位点.     

Relationship between adult height and body weight and risk of carotid atherosclerosis assessed in terms of carotid intima-media thickness: The Nagasaki Islands study

Background

Previous studies have reported an inverse association between height and risk of cardiovascular disease. However, evidence is limited for the association between risk of atherosclerosis and height. Further, although the association between atherosclerosis and body mass index (BMI) is reportedly positive, there have been no reports of studies on associations between height and atherosclerosis in relation to BMI.

Methods

We conducted a cross-sectional study of Japanese men aged 30 to 89 years undergoing general health check-ups.

Results

Of the 1,337 men, 312 were diagnosed with carotid atherosclerosis (carotid intima-media thickness (CIMT) ≥ 1.1 mm), but no significant association was found between height and carotid atherosclerosis for the entire study group. Stratification by BMI status of those analytical findings disclosed a significant inverse association between height and carotid atherosclerosis among overweight (BMI ≥ 25 kg/m²) but not among non-overweight (BMI < 25 kg/m²) men. The classical cardiovascular risk factors-adjusted odds ratio (OR) and 95% confidence interval (CI) of carotid atherosclerosis for an increment of one SD (standard deviation) in height (6.70 cm) were 0.71 (0.54 to 0.94) for overweight (BMI ≥ 25 kg/m²) and 1.05 (0.87 to 1.27) for non-overweight (BMI < 25 kg/m²) men.

Conclusion

Independent from classical cardiovascular risk factors, height was found to be inversely associated with carotid atherosclerosis for overweight but not for non-overweight men.     

SNP rs2243828 in MPO associated with myeloperoxidase level and atrial fibrillation risk in Chinese Han population

Previous studies shown that myeloperoxidase (MPO) level is higher in patients with atrial fibrillation (AF); however, no genetic evidence between MPO and AF risk in human population was observed. Therefore, the present study was aimed to investigate the association between rs2243828, a variant in promoter region of MPO and the risk of AF in Chinese GeneID population. The results demonstrated that the minor G allele of rs2243828 showed a significant association with AF in two independent population (GeneID‐north population with 694 AF cases and 710 controls, adjusted P_‐adj = 6.25 × 10^?3 with an odds ratio was 0.77, GeneID‐central population with 1106 cases and 1501 controls, P_‐adj = 9.88 × 10^?5 with an odds ratio was 0.75). The results also showed G allele was significantly associated with lower plasma concentration of myeloperoxidase in general population. We also observed a significant difference of odds ratio between subgroups of hypertension and non‐hypertension. Therefore, our findings identified variant in MPO associated with risk of AF and it may give strong evidence to link the inflammation with the incidence of AF.     

The role of PRKCH gene variants in coronary artery disease in a Chinese population

The aim of the present study was to assess the influences of PRKCH gene variants (1425G/A and _15) on the risk of coronary artery disease (CAD) in a Chinese population. Our study population consisted of 470 CAD patients and 434 control subjects. The alleles frequencies of the two variants were significantly higher among CAD patients than control subjects (P = 0.001 for 1425G/A and P = 0.001 for _15, respectively). In the CAD group, the A allele carriers of 1425G/A and _15 polymorphisms had higher low-density lipoprotein cholesterol (LDL-C) levels than homozygote G allele carriers (P = 0.001 and P = 0.021, respectively). In a multiple logistic regression model adjusted for age, sex, body mass index (BMI), etc., a markedly increased risk of developing CAD was found in subjects carrying GA or AA genotype (P = 0.005 and P = 0.018, respectively). In conclusion, we observed that there was a remarkable association of minor alleles (1425G/A and _15) in the PRKCH gene with an elevated risk of CAD and increased levels of LDL-C in this Chinese population.     

The ZC3HC1 rs11556924 polymorphism is associated with increased carotid intima-media thickness in patients with rheumatoid arthritis

Introduction

Rheumatoid arthritis (RA) is a complex polygenic disease associated with chronic inflammation, accelerated atherosclerosis and increased cardiovascular (CV) mortality. A recent meta-analysis has described the ZC3HC1 rs11556924 polymorphism as one of the most important signals associated with coronary artery disease (CAD) in non-rheumatic Caucasian individuals. In this study we evaluated the potential association of this gene polymorphism with subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in RA patients.

Methods

This study included 502 RA patients from Northern Spain. The ZC3HC1 rs11556924 polymorphism was genotyped with TaqMan single-nucleotide polymorphism (SNP) genotyping assays (C__31283062_10) in a 7900HT real-time polymerase chain reaction (PCR) system. cIMT was also assessed in these patients by carotid ultrasonography (US) technology.

Results

RA patients carrying the TT genotype had significantly higher cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.76 ± 0.18 mm and mean ± SD: 0.71 ± 0.16 mm respectively; P = 0.03) even after adjusting the results for sex, age at the time of US study, follow-up time and traditional CV risk factors (P = 0.04) evidencing that the effect conferred by ZC3HC1 rs11556924 polymorphism is independent of the traditional CV risk factors.

Conclusion

Our results indicate that ZC3HC1 rs11556924 polymorphism is associated with subclinical atherosclerosis in RA.     

The relationships of markers of cholesterol homeostasis with carotid intima-media thickness

Background

The relationship of cholesterol homeostasis and carotid intima-media thickness (cIMT) is unknown. To address this, we assessed markers of cholesterol homeostasis (serum plant sterols and cholesterol precursor concentrations as surrogate measures of cholesterol absorption and synthesis, respectively) and cIMT in a middle-aged, statin-naive population.

Methods

In this prospective study of primary prevention cIMT was measured by ultrasound in 583 hospital employees aged 25–60 years without prevalent cardiovascular disease or lipid-modifying medication. The serum concentrations of plant sterols (as markers of cholesterol absorption) were measured by gas-liquid chromatography. Lathosterol serum concentrations were quantitated to assess hepatic cholesterol synthesis.

Results

cIMT correlated positively with serum cholesterol (r = 0.22, P<0.0005) and lathosterol-to-cholesterol (r = 0.18, P<0.001). In contrast, plant sterols, as markers of cholesterol absorption, showed a weak negative correlation to cIMT measurements (r = −0.18; P<0.001 for campesterol-to-cholesterol). Stratifying subjects by serum sterol levels, we found that cIMT increased continuously over quintiles of serum cholesterol (P<0.0005) and was positively associated to serum lathosterol-to-cholesterol levels (P = 0.007), on the other hand, plant sterol levels showed a weak negative association to cIMT (P<0.001 for campesterol-to-cholesterol).

Conclusions

In this population without prevalent cardiovascular diseases or lipid-modifying medication, markers of increased endogenous cholesterol synthesis correlated positively with cIMT, while markers of cholesterol absorption showed a weakly negative correlation. These data suggest that not only total serum cholesterol levels but also differences in cholesterol homeostasis are associated with cIMT.     

The Per2 polymorphism rs10462023 is associated with the risk of stroke in a Chinese population

The key clock protein Period2 (Per2) has been suggested to play an essential role in regulating endothelial function. It also regulates the expression of plasminogen activator inhibitor-1, but its role in stroke development has not been studied. To explore the possible association between Per2 and ischemic stroke (IS), 479 Chinese IS patients and 306 healthy controls were recruited, and five tag single nucleotide polymorphisms representing the Per2 locus were genotyped using the Sequenom MassARRAY system. A significant difference was observed in the genotypic distribution (p = 0.014) and allele frequency (p = 0.005) of rs10462023, with carriers of the G allele being more prone to developing IS. After adjusting for possible risk factors including smoking, alcohol use, and history of hypertension and diabetes, a significant association was still apparent. Haplotype analysis also supported the association between Per2 and IS. This study suggests that Per2 variations are associated with IS and may represent genetic risk factors for IS in a Chinese population.     

Carotid artery intima-media thickness, carotid plaque and coronary heart disease and stroke in Chinese

Background

Our aim was to prospectively investigate the association between carotid artery intima-media thickness (IMT) as well as carotid plaque and incidence of coronary heart disease (CHD) and stroke in Chinese, among whom data are limited.

Methods and Findings

We conducted a community-based cohort study composed of 2190 participants free of cardiovascular disease at baseline in one community. During a median 10.5-year follow up, we documented 68 new cases of coronary heart disease and 94 cases of stroke. The multivariate relative risks (RRs) associated with a change of 1 standard deviation of maximal common carotid IMT were 1.38 (95% confidence interval [CI], 1.12–1.70) for CHD and 1.47 (95% CI, 1.28–1.69) for stroke. The corresponding RRs with internal carotid IMT were 1.47 (95% CI, 1.21–1.79) for CHD and 1.52 (95% CI, 1.31–1.76) for stroke. Carotid plaque measured by the degree of diameter stenosis was also significantly associated with increased risk of CHD (p for trend<0.0001) and stroke (p for trend<0.0001). However, these associations were largely attenuated when adjusting for IMT measurements.

Conclusions

This prospective study indicates a significant association between carotid IMT and incidence of CHD and stroke in Chinese adults. These measurements may be useful for cardiovascular risk assessment and stratification in Chinese.     

Significant association of SNP rs2106261 in the ZFHX3 gene with atrial fibrillation in a Chinese Han GeneID population

Atrial fibrillation (AF) is the most common cardiac rhythm disorder at the clinical setting and accounts for up to 15% of all strokes. Recent genome-wide association studies (GWAS) identified two single nucleotide polymorphisms (SNPs), rs2106261 and rs7193343 in ZFHX3 (zinc finger homeobox 3 gene) and rs13376333 in KCNN3 (encoding a potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3) that showed significant association with AF in multiple populations of European ancestry. Here, we studied a Chinese Han, GeneID cohort consisting of 650 AF patients and 1,447 non-AF controls to test whether the GWAS findings on ZFHX3/KCNN3 and AF can be expanded to a different ethnic population. No significant association was detected for rs7193343 in ZFHX3 and rs13376333 in KCNN3. However, significant association was identified between rs2106261 in ZFHX3 and AF in the GeneID population for both allelic frequencies (P=0.001 after adjusting for covariates of age, gender, hypertension, coronary artery disease, and diabetes mellitus; OR=1.32), and genotypic frequencies assuming either an additive or recessive model (OR=1.29, P=0.001 and OR=1.77, P =0.00018, respectively). When only lone AF cases were analyzed, the association remained significant (OR=1.50, P=0.001 for allelic association; OR=1.45, P=0.001 for an additive model; OR=2.24, P=0.000043 for a recessive model). Our results indicate that rs2106261 in ZFHX3 confers a significant risk of AF in a Chinese Han population. The study expands the association between ZFHX3 and AF to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of the 16q22 AF locus.     

Gelsolin rs1078305 and rs10818524 polymorphisms were associated with risk of oral squamous cell carcinoma in a Chinese Han population

Background: Gelsolin (GSN) is one of the most abundant actin-binding proteins, and is involved in cancer development and progression.

Patients and methods: A hospital-based case-control study including 201 patients with OSCC and 199 healthy controls was conducted. Seventeen single-nucleotide polymorphisms (SNPs) of GSN were investigated by Sequenom Mass ARRAY and iPLEX-MALDI-TOF technology.

Results: Through comparison of the 17 SNPs on GSN gene between the two groups, SNP rs1078305 and rs10818524 were verified to be significantly associated with an increased risk of OSCC. For GSN rs1078305, the TT genotype was associated with increased risk for OSCC (OR?=?1.92, 95% CI?=?1.11–3.32, p?=?0.028). CT/TT variants were also associated with increased risk for OSCC compared to the CC genotype (OR?=?1.83, 95% CI?=?1.25–3.84, p?=?0.032).

Conclusion: The rs1078305 and rs10818524 SNPs of GSN were associated with increased risk for OSCC development in a Chinese Han population.     

The common SNP (rs9939609) in the FTO gene modifies the association between obesity and high blood pressure in Chinese children

Previous studies have suggested that common variants in fat mass- and obesity-associated (FTO) gene are associated with body mass index (BMI) and the risk of obesity. Since obesity plays an important role in the etiology of high blood pressure (HBP), we aim to investigate the association between obesity and HBP in a population with different variants of the FTO gene. A total of 3,494 children (1,775 boys, 50.8 %) aged 6–18 years were recruited for measuring pubertal status, BMI and systolic and diastolic blood pressure. The single nucleotide polymorphism rs9939609 of the FTO gene was genotyped. The blood pressure levels increased by 1.4, 1.5 and 1.8 mmHg for systolic blood pressure and 0.8, 0.9 and 1.2 mmHg for diastolic blood pressure per 1-unit BMI increase in subjects carrying TT, TA and AA genotypes, respectively. After stratifying for FTO rs9939609 genotypes (TT, TA and AA), the odds ratios (95 % confidence intervals) of HBP in obese versus non-obese children were 4.26 (3.18–5.71), 5.13 (2.96–8.90) and 10.37 (1.59–67.43), respectively, with adjustment for age, gender and pubertal status. The FTO rs9939609 SNP modifies the effect of obesity on HBP in Chinese children, with obese ones carrying the AA homozygous genotype of the FTO rs9939609 having the highest risk of developing HBP.     

Association between OLR1 K167N SNP and intima media thickness of the common carotid artery in the general population

Background and Purpose

The lectin-like oxidised LDL receptor-1 (OLR1) gene encodes a scavenger receptor implicated in the pathogenesis of atherosclerosis. Although functional roles have been suggested for two variants, epidemiological studies on OLR1 have been inconsistent. Methods - We tested the association between the non-synonymous substitution K167N (rs11053646) and intima media thickness of the common carotid artery (CCA-IMT) in 2,141 samples from the Progression of Lesions in the Intima of the Carotid (PLIC) study (a prospective population-based study).

Results

Significantly increased IMT was observed in male carriers of the minor C (N) allele compared to GC and GG (KN and KK) genotype. Functional analysis on macrophages suggested a decreased association to Ox-LDL in NN carriers compared to KN and KK carriers which is also associated with a reduced OLR1 mRNA expression. Macrophages from NN carriers present also a specific inflammatory gene expression pattern compared to cells from KN and KK carriers.

Conclusions

These data suggest that the 167N variant of LOX-1 receptor affects the atherogenic process in the carotid artery prior to evidence of disease through an inflammatory process.     

Association of resistin (rs3745367) and urotensin II (rs228648 and rs2890565) gene polymorphisms with risk of type 2 diabetes mellitus in Indian population

Molecular Biology Reports - Insulin resistance may become the most powerful predictor of future development of type 2 diabetes mellitus (T2DM) and a therapeutic target for the treatment of the...     

Soluble FcgammaRIIIa(Mphi) levels in plasma correlate with carotid maximum intima-media thickness (IMT) in subjects undergoing an annual medical checkup

Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express FcgammaRIIIa (CD16) identical to that in NK cells, but with a cell type-specific glycosylation, and these soluble forms (sFcgammaRIIIa) are present in plasma. We measured sFcgammaRIIIa(Mphi) derived from macrophages in plasma from subjects undergoing an annual medical checkup. The levels of sFcgammaRIIIa(Mphi) increased with age, and correlated positively with body mass index, blood pressure, LDL cholesterol to HDL cholesterol ratio, triglycerides, hemoglobin A1c, and creatinine, but negatively with HDL-cholesterol levels. The sFcgammaRIIIa(Mphi) levels were related to the number of risk factors for atherosclerosis: such as aging, current smoking, diabetes, hypertension, hyper-LDL-cholesterolemia, hypo-HDL-cholesterolemia, and family history of atherosclerotic diseases. In addition, the sFcgammaRIIIa(Mphi) levels were correlated with carotid maximum intima-media thickness (IMT). These findings indicate the macrophages are activated during the incipient stage of atherosclerosis, and suggest sFcgammaRIIIa(Mphi) may be used as a predictive marker for atherosclerosis.     

Association of natural intake of dietary plant sterols with carotid intima-media thickness and blood lipids in Chinese adults: a cross-section study

Background

Many studies showed a moderate cholesterol-lowering effect of plant sterols (PS), but increased circulating PS might be atherogenic. We evaluated the associations between natural dietary intake of PS and carotid intima–media thickness (IMT) and serum lipids.

Methodology/Principal Findings

This community-based cross-sectional study included 1160 men and 2780 women aged 31–75 years. Dietary intakes were assessed using a food-frequency questionnaire. The IMTs at the common, bifurcation and internal carotid artery segments, and fasting serum total (TC), LDL (LDLc) and HDL (HDLc) cholesterol, and triglycerides (TG) were determined. After adjusting for potential covariates, multivariate analysis showed a dose-dependent inverse association of total PS intake with serum TC, LDLc, non-HDLc in women (P<0.001) and in men (P<0.05). As compared to the lowest quartile of PS intake (<206 mg/d), the multivariate-adjusted means of TC, LDLc and non-HDLc in the highest quartile of PS intake (447 mg/d) decreased by 5.0%, 6.2% and 6.5% in women (P<0.005), and by 6.4%, 7.1% and 6.7% (P>0.05) in men. Although the IMTs tended to be lower with greater intake of dietary PS, only small differences in the left internal IMT between the highest and lowest groups were observed among men (−7.6%) and women (−5.1%) (P<0.05). The multivariate analysis showed no significant mean differences among the PS groups in HDLc, TG and IMTs at other studied sites among men and women (all P>0.05).

Conclusions

Greater PS consumption from natural diets is associated with lower serum total, LDL, non-HDL cholesterol and with thinner left internal IMT in women and men.     

A comprehensive study of CD44 rs 187115 variant and cancer risk in a central Chinese population

The rs187115, an intronic variant of CD44 gene, has been previously reported to play a potential role in genetic susceptibility to cancer. Here, we comprehensively examined the association between CD44 rs187115 variant and cancer risk (breast cancer, cervical cancer, lung cancer, gastric cancer, liver cancer, colon cancer, and rectal cancer) in a central Chinese population. The rs187115 variant was genotyped with the polymerase chain reaction-restriction fragment length polymorphism assay. In this study, we observed that rs187115 was associated with the risk of cervical, lung, and liver cancer, but not with the risk of breast, gastric, colon, rectal or colorectal cancer. Of note, the G allele and G allele genotypes of rs187115 conferred an increased risk of cervical, lung, and liver cancer. To improve the statistical strength, a followed meta-analysis was conducted. The results demonstrated that rs187115 was significantly associated with cancer risk, and the significant association remained in the stratification analysis by ethnicity, genotyping method, and cancer type. Collectively, the CD44 rs187115 variant may be associated with the risk of cervical, lung, and liver cancer in the central Chinese population, and may be used as a potential biomarker for cancer predisposition in the Asian population, especially in the Chinese population.