Evidence of association between single-nucleotide polymorphisms in lipid metabolism-related genes and type 2 diabetes mellitus in a Chinese population

Background: Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder triggered by insulin resistance in peripheral tissues. Evidence has shown that lipid metabolism and related genetic factors lead to insulin resistance. Hence, it is meaningful to investigate the association between single-nucleotide polymorphisms (SNPs) in lipid metabolism-related genes and T2DM.Methods: A total of 1,194 subjects with T2DM and 1,274 Non-diabetic subjects (NDM) were enrolled. Five SNPs in three genes (rs864745 in JAZF1, rs35767 in IGF1, and rs4376068, rs4402960, and rs6769511 in IGF2BP2) that contribute to insulin resistance involving lipid metabolism were genotyped using the MassArray method in a Chinese population.Results: The allele and genotypes of rs6769511 in IGF2BP2 were associated with T2DM (P=0.009 and P=0.002, respectively). In inheritance model analysis, compared with the T/T-C/T genotype, the C/C genotype of rs6769511 in IGF2BP2 was a risk factor for the development of T2DM (P<0.001, odds ratio [OR] =1.76; 95% confidence interval [CI]: 1.29-2.42). Haplotype analysis revealed associations of the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 with the development of T2DM (P=0.015). Additionally, rs4376068C-rs4402960T-rs6769511C was a risk haplotype for T2DM (OR=1.179; 95% CI: 1.033-1.346).Conclusion: The rs6769511 in IGF2BP2 was associated with T2DM susceptibility, and the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 was associated with the development of T2DM in a Chinese population.     

Association Study of ARL15 and CDH13 with T2DM in a Han Chinese Population

Several studies indicate that plasma adiponectin levels are associated with the risk of type 2 diabetes mellitus (T2DM) or T2DM risk factors in diverse populations. In addition to the adiponectin gene, several other genes have been postulated to influence plasma adiponectin levels. In this study, we investigated two single nucleotide polymorphisms (SNPs), rs4311394 and rs4783244, located intronically in the ADP-ribosylation factor-like protein 15 (ARL15) and the T-cadherin (CDH13) genes, respectively. These SNPs were detected in a Han Chinese population using a TaqMan assay and evaluated for association with T2DM as well as with individual metabolic traits. Allele frequencies for rs4311394 were significantly different in T2DM and nondiabetes (NDM) groups (χ² = 4.49, P = 0.034). However, neither allele nor genotype frequencies for rs4783244 were associated with T2DM (χ² = 0.33, P = 0.56 and χ² = 2.35, P = 0.31 respectively). The SNPs did not exhibit significant association with individual metabolic traits in the T2DM and NDM groups. Our results indicated that the G allele of the rs4311394 might be a susceptibility factor for T2DM in the Han Chinese population (odds ratio: 1.20; 95% confidence interval: 1.01-1.41).     

Association of prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms and Alzheimer's disease in Chinese

Cyclooxygenase-2 (COX-2, encoded by the gene prostaglandin-endoperoxide synthase 2, PTGS2) is a key enzyme in the conversion of arachidonic acid to prostaglandins. The prostaglandins produced by COX-2 are involved in inflammation and pain response in different tissues in the body. Enhanced COX-2 expression had been found in regions of brains from patients with Alzheimer's disease (AD). Here, we proceeded to test the hypothesis that polymorphisms of the PTGS2 gene predispose to AD. IVS5−275 T>G and Ex10+837 T>C in addition to three tagging SNPs from HapMap database, which provided a comprehensive coverage of genetic variations in the PTGS2 gene in Chinese were genotyped among 257 AD patients and 244 age-matched healthy Chinese subjects. Genetic associations were analyzed by χ²-test and haplotypes analysis. Although the previously reported protective polymorphism (rs20417, −765 G/C) for AD in PTGS2 gene was not polymorphic in the Chinese population, SNPs in both the promoter (−2319 G>T) and 3′ region (Ex10+837 T>C) of PTGS2 were associated with the risk of AD (p = 0.01 and 0.03, respectively). Carriers of Ex10+837 T allele had a 1.5-fold increase in the risk of AD. This study suggested that PTGS2 gene was a predisposition gene and arachidonic acid metabolism might be involved in the pathogenesis of AD. It provided further evidence to support a role of inflammation in the development and progression of AD.     

2型糖尿病肺癌患者生存期影响因素分析

目的探讨2型糖尿病肺癌患者生存期及其影响因素。方法选取2014年至2016年在我院诊断的T2DM合并肺癌的患者43为观察组,同期诊断单纯肺癌不合并T2DM的患者40为对照组,查阅患者的一般资料,调查所有可能影响患者预后的危险因素,如年龄、性别、肺癌TNM分期、病理分型、远处转移、合并症、吸烟、治疗情况、血糖及控制血糖的方法等,随访患者的生存情况。结果观察组PFS时间为7.8±5.1月,对照组PFS时间为11.1±6.1月,观察组PFS时间明显短于对照组;观察组OS时间为15.0±7.5月,对照组OS时间为18.5±8.8月,观察组OS时间明显短于对照组。Cox回归分析发现,患者生存时间与是否合并糖尿病、远处转移、病理分期有关,差异具有统计学意义(P<0.05),而年龄、性别、是否吸烟、病理分型等对总生存期的影响较差,差异无统计学意义((P>0.05),Kaplan-Meier分析结果显示:合并T2DM的肺癌患者PFS明显低于单纯未合并T2DM的肺癌患者,远处转移的的肺癌患者PFS明显低于无远处转移的肺癌患者,IV期的肺癌患者低于II期的肺癌患者,II期肺癌患者低于I期的肺癌患者。结论T2DM合并肺癌无论是无进展生存期还是总生存期均低于单纯肺癌不合并T2DM的患者,T2DM合并肺癌患者除了传统的因素如远处转移、肿瘤TNM分期等影响肺癌患者的预后外,T2DM也是影响肺癌患者预后的独立危险因素。     

Association analysis of vitamin D receptor gene polymorphisms in North England population with Type 2 diabetes mellitus

BackgroundNumerous diabetes susceptibility loci, include a region consisting vitamin D receptor gene found in chromosome 12q, have been known using genome wide screens.AimThe aim of present study is to probe the relationship between polymorphism of vitamin D receptor gene (single nucleotide polymorphisms) and type 2 diabetes mellitus (T2DM). Five hundred T2DM patients and 200 healthy subjects with normal HbA1c (≤ 5.0 %), fasting blood sugar (≤ 120 mg/dL) and random blood sugar (≤ 140 mg/dL) were enrolled.MetholodgyThe genotypes were found by polymerase chain reaction restriction fragment length polymorphism and DNA sequencing.Resultsrevealed that no considerable differences in frequencies of genotype and allele of the Bsm I and Fok I polymorphisms between healthy and patients in the North England (For Fok I: OR = 1.11, 95% CI: 0.72–1.12; for Bsm I: OR = 1.35, 95% CI: 0.79–1.98).ConclusionIt is recommended that both following polymorphisms of vitamin D receptor gene may not considerably add to the progression of T2DM in the North England.     

Association of eotaxin-2 gene polymorphisms with plasma eotaxin-2 concentration

Chemokine (C–C motif) ligand 24 (CCL24, eotaxin-2) is a CC chemokine that recruits and activates cells bearing the CC chemokine receptor 3, which play a major role in asthma. Previously, we observed a significant association between a single nucleotide polymorphism (SNP) in eotaxin-2 (CCL24+1272A G) and a lower risk of asthma. Consequently, this study has followed up on those genetic effects by evaluating the association between the SNP and plasma eotaxin-2 concentration in 172 asthmatics and 135 normal controls. Asthmatics had significantly higher plasma eotaxin-2 levels than did normal controls (P=0.02). The SNP (CCL24+1272A G) and two haplotypes (ht2 and ht6) were strongly associated with plasma eotaxin-2 levels in asthmatics (CCL24+1272A G: P=0.006, ht2: P=0.006, and ht6: P=0.002). The CCL24+1272A G allele and the ht2 and ht6 haplotypes showed a gene–dose effect on the plasma eotaxin-2 levels in asthmatics (P=0.005–0.032). In conclusion, the susceptibility of patients with asthma to high eotaxin-2 production may be due to genetic effects of the CCL24+1272A G polymorphism, ht2 and ht6 haplotypes.     

Association analysis of PON polymorphisms in sporadic ALS in a Chinese population

Single nucleotide polymorphisms (SNPs) of the paraoxonase gene family (ordered PON1, PON2, and PON3) have been associated with the risk of developing sporadic amyotrophic lateral sclerosis (SALS) in Caucasian populations. However, this association has yet to be confirmed in Chinese SALS patients. Nine SNPs across the PON gene cluster (i.e., rs662, rs705381, rs705382, rs854548, rs854560, rs7493, rs11981433, rs757158, and rs10487132) were analyzed in a large cohort consisting of 373 SALS patients and 248 controls from Southwest China. The data from the present study suggest that these SNPs of the PON gene cluster do not contribute to the risk for developing SALS in a Chinese population.     

Association of ABCG2 polymorphisms with ischemic stroke in a Chinese population

ATP‐binding cassette, superfamily G, member 2 (ABCG₂) has been shown to play an important role in the development of ischemic stroke in European and African American populations. The aim of the present study is to test the hypothesis that there are associations between ABCG₂ polymorphisms and ischemic stroke risk in a Chinese population. We conducted a case–control study including 967 participants with ischemic stroke and 939 stroke‐free controls. The rs2231137C > T and rs2231142G > T were genotyped using a TaqMan real‐time polymerase chain reaction assay. We found the rs2231137C > T and rs2231142G > T in ABCG₂ were significantly associated with ischemic stroke (sex‐, age‐, BMI‐, SBP‐, DBP‐adjusted OR = 1.252; 95% CI, 1.035–1.515; P‐value = 0.021 and OR = 1.526; 95% CI, 1.085–2.146; P‐value = 0.015, respectively). By haplotype analyses, the haplotype T‐G still had a strongly significant association with ischemic stroke (OR = 0.806; 95% CI, 0.692–0.939; P‐value = 0.00568). Our findings identified the rs2231137C > T and rs2231142G > T polymorphisms of the ABCG₂ as risk factors for ischemic stroke in a Chinese population.     

Association of two polymorphisms rs2910164 in miRNA-146a and rs3746444 in miRNA-499 with rheumatoid arthritis: A meta-analysis

Background

It has been reported that two single nucleotide polymorphisms (SNPs) rs2910164 in miRNA-146a and rs3746444 in miRNA-499 might be associated with the susceptibility to rheumatoid arthritis (RA). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and RA risk.

Methodology/main results

A systematic search of studies on the association of two SNPs with susceptibility to RA was conducted in PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. A total of 6 case-control studies on rs2910164 and 3 studies on rs3746444 were included. Though no evidence of association was found between rs2910164 polymorphism and RA risk in all the genetic models, a trend of reduced risk could be drawn. (C versus G: OR = 0.93, 95% CI 0.82–1.05; GC versus GG: OR = 0.89, 95% CI 0.73–1.10; CC versus GG: OR = 0.84, 95% CI 0.64–1.10; GC/CC versus GG: OR = 0.89, 95% CI 0.73–1.08; CC versus GC/GG: OR = 0.94, 95% CI 0.77–1.14). A significant increased risk of RA was observed in the rs3746444 polymorphism in homozygote comparison, recessive comparison, and allele comparison, but there was insufficient data to fully confirm the association of RA and rs3746444 in miRNA-499.

Conclusions

MiRNA-146a rs2910164 polymorphism is not associated with RA risk, while miRNA-499 rs3746444 polymorphism is correlated with RA risk. However, the results of miRNA-499 rs3746444 should be interpreted with caution due to limited sample and heterogeneity. Large-scale and well-designed studies are needed to validate our findings.     

中国汉族人群2型糖尿病易感性相关基因多态性

2型糖尿病(type 2 diabetes mellitus,T2DM)的发病与多个基因累加效应及多种环境因素相关.已在中国汉族人群中研究过的与T2DM易感性相关的基因多态性包括:全基因组相关研究中的CDKAL1、CDKN2A/B、SLC30A8、IGF2BP2、HHEX、FTO 以及KCNQ1基因;脂联素基因;核呼吸因子基因;葡萄糖激酶基因;肿瘤坏死因子α基因等.探索这些易感基因可以为人类治疗T2DM起到极大的推动作用.但至今已明确的基因依然很少,国内外的研究结果不尽相同,尚需进一步地深入研究.     

北方地区汉族消化道疾病中CYP2C19基因多态性分析

目的探讨中国北方地区汉族消化道疾病患者中CYP2C19基因多态性的频率分布及其与消化道疾病的相关性。方法采用数字荧光分子探针杂交法测定1 429例北方汉族消化道疾病的CYP2C19基因型,并根据其药物代谢活性分为超快代谢(ultra-rapid metabolizer,UM)型、快代谢(extensive metabolizer,EM)型、中间代谢(intermediate metabolizer,IM)型和慢代谢(poor metabolizer,PM)型四种。结果 CYP2C19等位基因*1、*2、*3和*17的频率分别为64.3%、29.7%、4.9%和1.0%。CYP2C19 UM型患者占1.2%(17例),EM型占41.5%(593例),IM型占45.3%(647例),PM型占12.0%(172例)。幽门螺旋杆菌总体感染阳性率为75.3%,不同CYP2C19代谢型患者的感染阳性率差异无统计学意义。在非萎缩性胃炎、萎缩性胃炎、消化性溃疡、反流性食管炎、Barrett食管和胃癌等消化道疾病之间CYP2C19的代谢型分布差异无统计学意义。10例胃癌患者中有8例为IM型。结论 CYP2C19 IM型和EM型是北方地区汉族消化道疾病中常见的代谢类型,CYP2C19*2、*3及PM型的频率高于欧洲人群,而CYP2C19*17及UM型频率低于欧洲人群。     

牡丹江地区Ⅱ型糖尿病人群中INSR基因第8外显子NsiⅠ酶切多态分析

目的探讨INSR基因第8外显子多态与牡丹江地区Ⅱ型糖尿病的相关性。方法采用PCR-RFLP技术,对176例牡丹江Ⅱ型糖尿病患者、148例正常人的INSR基因多态性检测,观察基因型频率及等位基因频率。结果Ⅱ型糖尿病组N1N1、N1N2、N2N2基因型频率分别为70.5%、28.4%、1.1%;N1及N2等位基因频率分别为84.7%、15.3%。正常对照组N1N1、N1N2、N2N2基因型频率分别为62.2%、28.4%、9.4%;N1及N2等位基因频率分别为76.4%、23.6%。两组之间基因型频率及等位基因频率差异有统计学意义(P<0.01)。Ⅱ型糖尿病组N2基因的频率明显低于正常对照组。结论 INSR基因多态性与牡丹江地区的Ⅱ型糖尿病发病有相关性,是II型糖尿病的主要致病基因。     

长沙市三甲医院T2DM患者健康素养与授权能力相关性分析

目的 探讨2型糖尿病（T2DM）患者健康素养与授权能力的相关性,为糖尿病有效管理提供参考。方法 采用便利抽样法,对在长沙市两所三甲医院治疗的152例T2DM住院患者使用一般资料调查表、慢性病病人健康素养量表和糖尿病授权简化中文量表进行问卷调查。结果 152例T2DM患者健康素养水平总分为（100.55±11.41）分,授权能力为（3.68±0.61）分;相关分析显示两者呈正相关（P＜0.01）。结论 临床医护人员在对住院患者实施相关干预前,应先仔细评估患者健康素养,帮助提高其授权能力,以便患者能更好认识到自身问题,做出健康决策与行动。     

Genetic polymorphisms and phenotypic analysis of drug-metabolizing enzyme CYP2C19 in a Li Chinese population

CYP2C19 is a highly polymorphic gene and CYP2C19 enzyme results in broad inter-individual variability in response to certain clinical drugs, while little is known about the genetic variation of CYP2C19 in Li Chinese population. The aim of this study was to identify different CYP2C19 mutant alleles and determine their frequencies, along with genotype frequencies, in the Li Chinese population. We used DNA sequencing to investigate promoter, exons, introns, and 3’UTR of the CYP2C19 gene in 100 unrelated healthy Li individuals from Hainan Province, China. We also used SIFT and PolyPhen-2 to predict the protein function of the non-synonymous mutation in CYP2C19 coding regions. We identified 22 different CYP2C19 polymorphisms in the Li Chinese population, including three novel variants (-254A > G, 17807T > C and 58025C > T). The allele frequencies of CYP2C19*1A, *1B, *2A and *3A were 50%, 24%, 24.5%, and 1.5%, respectively. The most common genotype combinations were *1A/*1B (48%) and *1A/*2A (49%). Additionally, the mutation Ala161Pro was predicted to be intolerant and possibly damaging by SIFT and PolyPhen-2, respectively. Our results shed new light on CYP2C19 polymorphisms in Li individuals, which may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group.     

牡丹江地区II型糖尿病人群中ACE基因多态分析

目的研究牡丹江地区II型糖尿病与A;;CE基因多态的相关性。方法采用PCR-RFLP技术,对牡丹江汉族II糖尿病患者、正常人的A;;CE基因多态性检测,观察基因型频率及等位基因频率。结果 II型糖尿病组II、ID、DD基因型频率分别为65.5%、26.4%、8.0%;I及D等位基因频率分别为78.7%、21.3%。正常对照组II、ID、DD基因型频率分别为35.0%、55.0%、10.0%;I及D等位基因频率分别为62.5%、37.5%。两组之间基因型频率及等位基因频率差异有统计学意义（P〈0.01）。结论 A;;CE基因多态性与牡丹江地区的II型糖尿病发生有相关性。     

中国广西人群中RTN4基因遗传多态性的研究

目的:研究RTN4基因rs2920891A/C和rs17046647A/G位点多态性在广西人群中的分布特征,比较不同人群的分布差异。方法:本实验采用多重单碱基延伸PCR(SNa Pshot)和DNA测序方法,对323例广西健康体检者RTN4基因的rs2920891A/C和rs17046647A/G位点基因型进行检测,并与国际人类基因组单体型图计划(Hap Map)公布的不同人群(北京、日本、欧洲及非洲人群)RTN4基因多态性数据进行比较。结果:在广西人群中,RTN4基因rs2920891A/C位点存在AA、AC、CC基因型及A、C等位基因,其等位基因频率在男女间的分布差异有统计学意义(P0.05),基因型及等位基因频率与日本、欧洲及非洲人群比较差异均有统计学意义(P0.05);rs17046647A/G位点存在AA、AG、GG基因型和A、G等位基因,基因型及等位基因频率在男女间比较差异无统计学意义(P0.05),而与日本、欧洲及非洲人群比较差异均有统计学意义(P0.01)。结论:中国广西人群中RTN4基因的rs2920891A/C和rs17046647A/G位点多态性与其他种族间存在差异性。     

Association of polymorphisms in pre-miRNA with inflammatory biomarkers in rheumatoid arthritis in the Chinese Han population

The aim of this study was to detect the association between 2 single nucleotide polymorphisms (SNPs), rs2910164 G>C and rs3746444 T>C, in pre-miRNA (hsa-mir-146a and hsa-mir-499) and the chronic inflammation in the Chinese Han population with rheumatoid arthritis (RA). Two hundred sixty-two Han Chinese patients with RA were recruited in this study. The SNPs were genotyped by polymerase chain reaction restriction fragment length polymorphism. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the plasma concentrations of interleukin (IL)-6, tumor necrosis factor α (TNF-α), and transforming growth factor β1 (TGF-β1) were measured. There was a significant difference in the levels of CRP and ESR among different genotypes in rs3746444 (p = 0.031 and p = 0.047, respectively). The heterozygote CT had significantly higher levels of CRP and ESR compared with homozygotes CC and TT. No significant association was observed between the SNP rs2910164 and the levels of CRP, ESR, IL-6, TNF-α, and TGF-β1 (all p > 0.05). The results of this study provided the first evidence that the SNP rs3746444 in pre-miR-499 could affect the inflammatory reaction in patients with RA. The findings were significant and might contribute to the clinical assessment of inflammatory activity, which in turn may influence therapeutic decision making.     

SH2B3基因标签单核苷酸多态性与汉族原发性高血压的关系

目的探讨SH2B衔接蛋白3(SH2B3)基因标签单核苷酸多态(SNPs)与汉族原发性高血压(EH)的关系。方法用聚合酶链式反应-限制性片段长度多态性方法(PCR-RFLP),对1 020例汉族人(EH患者和对照者各510例)SH2B3基因6个标签SNPs(rs7309325、rs11065898、rs10849947、rs2239196、rs2238154和rs739496)的多态性进行检测,运用遗传模型分析该基因与汉族EH的相关性。结果 rs2239196位点基因型和等位基因在EH组和对照组间的频率分布均具有显著性差异(Bonfferoni校正P0.05),Logistic回归分析结果显示T等位基因携带者的患病风险显著升高(OR=2.59,95%CI 1.36~4.96,Bonfferoni校正P0.05)。结论 SH2B3基因rs2239196位点T等位基因可能是汉族EH发生的危险因子。     

Association of NCOA2 gene polymorphisms with obesity and dyslipidemia in the Chinese Han population

Background: Nuclear receptor coactivator 2 (NCOA2) gene plays an important role in adipogenesis and lipid metabolism. NCOA2 gene null mice exhibited less fat accumulation and lower serum lipid levels, and were protected against obesity. Few studies are known to have analyzed the association of NCOA2 gene single nucleotide polymorphisms with obesity and serum lipid profile. Our study aimed to evaluate the association of NCOA2 gene polymorphisms with the risk of obesity and dyslipidemia in the Chinese Han population. Methods: Two NCOA2 gene polymorphisms (rs41391448 and rs10504473) were selected and genotyped in a Chinese Han cohort with 529 participants. The effect of different genotypes on BMI and serum lipid levels (TG, TC, LDL-C and HDL-C) was performed by the analysis of covariance. Association of NCOA2 polymorphisms with obesity and dyslipidemia was assessed by odds ratios (OR) and 95% confidence intervals (CI) under the unconditional logistic regression analysis. Results: Significant association was observed between rs10504473 polymorphism and obesity under the recessive model (OR = 1.88, 95% CI 1.02-3.45, P = 0.047; adjusted OR = 1.87, 95% CI 1.02-3.44, P = 0.048). However, no association remained significant after Bonferroni correction. Conclusion: Our study suggests a possible association between NCOA2 rs10504473 polymorphism and obesity, and this SNP may influence the susceptibility of obesity in the Chinese Han population.