Lipoprotein lipase polymorphisms and responses to long-term overfeeding

OBJECTIVES: The role of the lipoprotein lipase (LPL) gene Hind III, S447X, Bam HI and Pvu II polymorphisms on body composition and lipid and lipoprotein changes in response to long-term overfeeding was studied. SUBJECTS: Twelve pairs of male monozygotic twins ate a 4.2 MJ day-1 energy surplus, 6 days a week, during a period of 100 days. RESULTS: Overfeeding induced a decrease in high-density lipoprotein 2 cholesterol (HDL2-C) and HDL2-C to HDL3-C ratio in the H2H2 (n = 12) subjects of the LPL Hind III polymorphism. In contrast, the H1H1/H1H2 (n = 12) subjects experienced increases both in the HDL2-C and HDL2-C to HDL3-C ratio (P = 0.009 and 0.007, respectively, for differences in percentage changes between H2H2 and H1H1/H1H2). In addition, the H2H2 genotype was associated with higher levels of very-low-density lipoprotein triglyceride (VLDL-TG) (P < 0.03) and VLDL-C (P < 0.05) before and after overfeeding and higher HDL-TG levels (P < 0.003) after overfeeding. Postheparin lipoprotein lipase (PH-LPL) activity tended to increase in H1H1/H1H2 and decrease in H2H2 subjects. The H2H2 subjects had lower total HDL-C than those with the genotype H1H1/H1H2 4 months and 5 years after overfeeding (P = 0.04 and 0.10, respectively). The plasma lipid differences were similar amongst subjects with the S447S (n = 4) genotype of the S447X and H2H2 genotype of the Hind III polymorphisms. Body composition changes in response to overfeeding were not different between the Hind III genotypes. LPL Pvu II and Hind III polymorphisms were associated weakly with body weight gain (P = 0.015-0.039) but strongly with adipose tissue LPL activity (P < 0.01) after the caloric surplus. CONCLUSIONS: We conclude that the H2H2 subjects of the LPL gene Hind III polymorphism experience a decrease in the concentration of antiaterogenic lipoproteins when they are exposed to long-term positive energy balance. This may have been partly caused by a diminished catabolism of TG-rich particles in H2H2 subjects. LPL Pvu II and Bam HI polymorphisms were associated with body weight gain and adipose tissue LPL activity. Genetic variation at the LPL locus could thus be one of the factors responsible for the inter-individual differences observed in plasma lipid and lipoprotein responses to chronic positive energy balance. It must be kept in mind that the sample size for this study was small. Nonetheless, it provides useful information on the genes and pathways that should be further explored.     

脂蛋白脂酶基因HindⅢ多态性与冠心病相关性的meta分析

目的对中国汉族人脂蛋白脂酶（LPL）基因HindⅢ多态性H＋H＋基因型与中国人群冠心病的相关性进行meta分析。方法制定文献的纳入标准,检索中国期刊全文数据库、万方数据库、维普信息数据库、PubMed及中国学术期刊博硕士学位论文全文数据库等关于LPL基因HindⅢ多态性与冠心病相关性的原始研究,评价纳入文献质量,进行meta分析。结果7项研究被纳入meta分析,其中冠心病患者1184例,对照组1004例。按Peto固定效应模型合并后,LPL基因的HindⅢ多态性H＋H＋基因型／（H＋H-／H-H＋）基因型的OR值为1．22,95％CI为1．02—1．46,P=0．03。结论LPL基因HindⅢ多态性可能与中国汉族人群冠心病发病有关。     

脂蛋白脂酶基因Ser447→终止密码突变多态性与缺血性脑血管病的关系

目的:探讨中国人群中脂蛋白脂酶Ser447→终止密码突变(Ser447Stop)多态性与缺血性脑血管病(ICVD)的相关性。方法:共纳入ICVD患者112例(短暂性脑缺血发作36例,脑梗死76例)和对照者105例,用聚合酶链反应和限制性片段长度多态性分析确定其基因型。结果:ICVD组CG GG基因型频率显著低于对照组(0·161比0·391,OR=3·3,95%CI1·1~7·8,P=0·002)。ICVD亚组分析表明,短暂性脑缺血发作组CG GG基因型频率与对照组无显著差异,而脑梗死与对照组却有显著差异。结论:脂蛋白脂酶基因Ser447Stop多态性与ICVD特别是脑梗死呈显著相关性,可能是ICVD的一种保护性因素。     

Lipoprotein lipase gene variants relate to presence and degree of microalbuminuria in Type II diabetes

AIMS/HYPOTHESIS: Lipids and lipoproteins, particularly triglyceride rich lipoproteins, could influence the development and progression of microalbuminuria in diabetes. Lipoprotein lipase gene variants have been found to correlate with lipid/lipoprotein concentrations, especially hypertriglyceridaemia. We assessed the influence of this gene on microalbuminuria in Type II (insulin-dependent) diabetes mellitus. METHODS: Microalbuminuria was determined quantitatively in 386 sequential Type II diabetic patients by measurement of the albumin-to-creatinine ratio (ACR). DNA was analysed for two common intronic LPL single nucleotide polymorphisms (Pvu II, intron 6, and Hind III, intron 8), and three common exonic mutations (Asp(9)-Asn, exon 2, Asn(291)-Ser, exon 6, and Ser(447)-Ter, exon 9). RESULTS: Individuals with P (2) P (2) (Pvu II) and H (2) H (2) (Hind III) genotypes had significantly greater ACRs ( P(2)P(2) vs P(1)P(1)+ P(1)P(2), 5.0+/-0.5 vs 3.4+/-0.3, p=0.0004 and H(2)H(2) vs H(1)H(1)+ H(1)H(2), 4.3+/-0.4 vs 3.4+/-0.3, p=0.04). Logistic regression analysis demonstrated that only the P(2)P(2) genotype ( p=0.0004), systolic BP ( p=0.008) and creatinine ( p=0.031) were independently associated with the presence of microalbuminuria/proteinuria. P(2) homozygotes were 170% more likely to have microalbuminuria or proteinuria, O.R. 2.7 (1.6-4.5, p=0.0001), 150% more likely to have microalbuminuria, O.R. 2.5 (1.5-4.3, p=0.001), and 330% more likely to have proteinuria, O.R. 4.3 (1.6-11.4, p=0.004). There were no associations of microalbuminuria with any of the exonic polymorphisms. CONCLUSION/INTERPRETATION: Genetic variants of lipoprotein lipase correlate with presence and severity of microalbuminuria in Type II diabetes, independent of effect on serum lipids. This association is only apparent in genetic variants demonstrating greatest heterozygosity.     

Association of lipoprotein receptor, receptor-associated protein, and metabolizing enzyme gene polymorphisms with gallstone disease: A case-control study.

INTRODUCTION: To identify high risk alleles for gallstone disease, we analyzed association of LDLRAvaII, LRPAP1 insertion/deletion, CETPTaqI B, and LPLHindIII polymorphisms with gallstone disease. METHODS: In DNA samples of 214 gallstone patients and 322 age and sex matched controls, specific region containing polymorphisms was PCR amplified and digested with restriction enzymes except for LRPAP1 insertion/deletion polymorphism. RESULTS: LRPAP1 gene insertion/deletion polymorphism was found to be significantly associated with gallstone disease. Genotype II was conferring significant risk for gallstone disease in females only (P=0.019; OR 2.577, 95% CI 1.144-5.806). LDLRAvaII, CETPTaqI B, and LPLHindIII polymorphisms were not found to be associated with gallstone disease either at genotype or allele level. CONCLUSIONS: LRPAP1, II genotype carrier females may have increased risk for gallstone disease. On the other hand, LDLR AvaII, CETP TaqI B, and LPL HindIII polymorphisms may not be associated with gallstone disease.     

2型糖尿病患者脂蛋白酯酶基因多态性与血甘油三酯水平的关系

目的 探讨2型糖尿病患者脂蛋白酯酶（LPL）常见基因多态性与血甘油三酯水平的关系.方法选取2008年6月至2010年4月郑州大学第一附属医院内分泌科初次住院的152例2型糖尿病患者为病例组,入选患者均符合1999年WHO诊断标准,以年龄、地区、性别频数匹配从河南省级医院体检人群中抽取145名健康体检者为对照组,对两组分别抽血提取DNA,PCR扩增LPL基因特定片段,限制性内切酶TaqⅠ、RsaⅠ和HinfⅠ、PvuⅡ进行酶切反应,分析酶切产物.聚丙烯酰胺凝胶电泳,分析电泳结果,所有患者均测定血甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A（ApoA）、载脂蛋白B（ApoB）、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、胰岛素抵抗指数（HOMA-IR）.统计学方法采用χ^2检验检测观察到的基因型是否符合遗传学平衡定律,组间血脂水平比较采用t检验,基因型频率和等位基因频率的差异比较用χ^2检验,以α=0.05作为检验水准.结果 LPL基因Ser447Ter位点中病例组G等位基因和CG基因型频率均低于对照组（3.3% vs 12.4%;6.6% vs 24.8%）,差异均有统计学意义（均P〈0.05）;病例组和对照组CG基因型携带者血TG水平均低于非携带者（分别为1.39±0.11 vs 1.68±0.18;1.24±0.08 vs 1.48±0.15;P〈0.05）,差异有统计学意义.对照组的CG基因型HDL-C高于CC基因型（1.46±0.06 vs 1.35±0.08;P〈0.05）,差异有统计学意义.病例组和对照组中均未发现Asp9Asn及Asn291Ser,两组间PvuⅡ酶切基因型出现频率差异无统计学意义.各组基因频率符合Hardy-Weinberg平衡定律吻合度检验.结论 我国河南汉族人群脂蛋白酯酶基因Asp9Asn、Asn291Ser、PvuⅡ酶切位点多态性与2型糖尿病无明显关联,而Ser447Ter多态性可以降低血TG水平,对于降低2型糖尿病发病而言可能是一个保护性突变.     

Effect of SstI polymorphism of the apolipoprotein CIII gene and environmental factors on risks of hypertriglyceridemia in Taiwan aborigines.

BACKGROUND: Hypertriglyceridemia (HTG) is a heterogeneous metabolic disorder. The aim of this study was to examine associations among genetic polymorphisms, SstI polymorphism of apolipoprotein CIII (ApoCIII) and Hind III polymorphism of lipoprotein lipase (LPL), environmental factors and risks of HTG. METHODS AND RESULTS: Two hundred and forty-nine southern Taiwanese aborigines were recruited for a cross-sectional study, which included 90 subjects with triglyceride (TG)>150 mg/dl (HTG) and 159 with TGor=25 (OR=2.22, 95% CI: 1.18-4.16), starchy food consumption>or=3 times/week (OR=1.89, 95% CI: 1.00-3.59) and ApoCIII S2S2 genotype (OR=3.35, 95% CI: 1.10-10.19) were independently (p<0.05) associated with HTG risks. Among ApoCIII S1S1, S1S2 and S2S2 genotypes, ApoCIII and TG concentrations increased (p<0.01) in a dose-responsive manner. CONCLUSIONS: The ApoCIII S2 variant and environmental factors, including education, tribal background, BMI and starchy food intake, modulate the risks of HTG in aboriginal Taiwanese. Interaction between genetic and environmental factors warrants further investigation.     

Heat shock protein gene 70-2 polymorphism is differentially associated with the clinical phenotypes of ulcerative colitis and Crohn's disease

BACKGROUND AND AIM: A single nucleotide polymorphism in heat shock protein 70-2 (HSP70-2) has been shown to be associated with a severe clinical course in Crohn's disease (CD), but it is not known if such a relationship exists in ulcerative colitis (UC). The aim of the present study was to identify associations between the HSP70-2 polymorphism and the clinical courses of CD and UC in Koreans. METHODS: Restriction fragment length polymorphism analysis was performed for HSP70-2 polymorphisms using the PstI-cleavage site present in the B allele but not in the A allele of the DNA obtained from 101 patients with CD, 144 patients with UC, and 245 age- and sex-matched healthy controls. Study subjects were classified by disease behavior, severity and extent of disease. RESULTS: In CD, multivariate analysis showed that the AA genotype of HSP70-2 polymorphisms was associated with non-perforating disease (OR 10.10, 95% CI 1.66-15.38) and male sex (OR 3.56, 95% CI 1.04-12.23), and that the BB genotype was associated with severe CD (OR 12.03, 95% CI 1.60-101.56). In contrast, multivariate analysis for UC showed that the AA genotype was associated with severe UC (OR 2.02, 95% CI 1.34-3.03). CONCLUSIONS: CD patients with BB genotype of HSP70-2 polymorphism tend to experience a more severe clinical course and allele A is associated with more severe UC. HSP70-2 polymorphism may be used to predict CD and UC phenotypes, which can illuminate immunological differences in CD and UC.     

过氧化物酶体增殖活化受体γ基因Pro12Ala和C161T多态性与溃疡性结肠炎的相关性

目的研究过氧化物酶体增殖活化受体γ（PPAR-γ）基因Pro12Ala和C161T位点的多态性与湖北汉族人群溃疡性结肠炎（UC）的相关性。方法采用多聚酶链式反应-限制片段长度多态性分析方法（PCR-RFLP）,对212例UC患者和220例健康对照者进行PPAR-γ基因分型。结果UC患者PPAR-γ基因C161T位点C／T基因型频率,T等位基因频率明显高于正常组（35．4％比25．0％,P=0．015,OR=1．69,95％CI=1．12～2．57;20．1％比12．9％,P=0．006,OR=1．68,95％CI=1．17～2．43）,T等位基因携带者也高于正常对照组（37．7％比25．5％,P=0．007,OR=1．77,95％CI=1．18～2．68）。而Pro12Ala位点基因型频率,等位基因频率UC组与对照组比较差异无统计学意义（P〉0．05）。结论PPAR-γ基因C161T位点基因T等位基因与湖北汉族人群UC的发生存在相关性。     

Multidrug resistance 1 gene polymorphism and susceptibility to inflammatory bowel disease

BACKGROUND: Several studies have evaluated the role of the multidrug resistance 1 gene (MDR1) polymorphism, which encodes the membrane-bound efflux transporter P-glycoprotein 170, in determining susceptibility to and disease behavior in inflammatory bowel disease (IBD), but with conflicting results. METHODS: A total of 211 patients with Crohn's disease (CD), 97 patients with ulcerative colitis (UC), and 212 control subjects were investigated for the presence of MDR1 G2677T/A and C3435T polymorphisms. Genotype frequencies of CD and UC patients were compared to those observed in a control population. Genotype-phenotype correlations with major clinical features were also established and estimated risks (odds ratio [OR] with 95% confidence interval [CI]) for the mutations were calculated by a logistic regression analysis and multiple correspondent analysis. RESULTS: No significant difference was observed for genotype frequencies for both MDR1 G2677T/A and C3435T polymorphisms on overall disease susceptibility for either CD or UC patients compared with control subjects. A significant association was found between the MDR1 C3435T polymorphism and patients with ileo-colonic CD (OR = 3.34; 95% CI: 1.34-8.27). Interestingly, a negative association was found between MDR1 C3435T polymorphism in patients with a positive family history for IBD (OR = 0.44; 95% CI: 0.20-0.95) and articular manifestations (OR = 0.29; 95% CI: 0.13-0.68). Both susceptible and protective effects were identified. No significant association between G2677T/A polymorphism and any specific subphenotypes was found, nor was there any association with subphenotypic categories of UC and both single nucleotide polymorphisms. CONCLUSIONS: The results of our study suggest that MDR1 gene polymorphism could have a role in determining susceptibility to IBD. The variability of this possible effect in the several studies reported so far may be the indirect expression of the complex role played by the MDR1 gene and its product, P-glycoprotein 170, in the regulation of host-bacteria interactions and in the pathogenesis of IBD.     

Genetic polymorphisms of CD14 and Toll-like receptor-2 (TLR2) in patients with ulcerative colitis

BACKGROUND AND AIM: Ulcerative colitis (UC) is a multifactorial disease resulting from a complex interaction of genetic and environmental factors. Identifying genetic variants that alter the innate immune response is highly relevant to understanding the pathogenesis of UC. The aim of this study was to investigate the association between CD14 and Toll-like receptor-2 (TLR2) genetic polymorphisms and chronic UC in Japanese patients. METHODS: The study population consisted of 102 chronic UC patients and 146 healthy control subjects. Polymorphisms in the promoter at C-260T of CD14 gene were investigated by PCR restriction fragment length polymorphism, and -196 to -174 del of TLR2 was investigated by allele-specific PCR. RESULTS: The frequencies of CD14 TT and T carrier were significantly higher in UC patients than in controls (TT: OR = 3.98, 95% CI 1.82-8.71, P = 0.0005; T carrier: OR = 2.98, 95% CI 1.47-6.01, P = 0.002). In addition, TT and T carrier were more closely associated with distal colitis phenotype (TT: OR = 7.78, 95% CI 2.14-28.28, P = 0.0007; T carrier: OR = 6.30, 95% CI 2.71-14.58, P = 0.005), onset after 20 years of age (TT: OR = 5.28, 95% CI 2.18-12.79; T carrier: OR = 3.79, 95% CI 1.67-8.59), chronic continuous type (TT: OR = 4.26, 95% CI 1.56-11.64; T carrier: OR = 3.09, 95% CI 1.33-7.82), and fewer than two hospitalizations (TT: OR = 4.44, 95% CI 1.81-10.89; T carrier: OR = 3.26, 95% CI 1.43-7.27). There was no significant difference in TLR2 -196 to -174 del/del and del/ins carrier frequencies between UC patients and healthy controls. However, these frequencies were significantly higher in steroid-dependant patients than in controls (del/del: OR = 6.08, 95% CI 1.41-26.21; del carrier: OR = 3.00, 95% CI 1.13-7.98). CONCLUSION: The results suggest that existence of a mutation in the CD14 gene is associated with an increased susceptibility to developing UC, especially chronic continuous distal colitis phenotypes that develop after 20 years of age. Furthermore, polymorphism of TLR2 may be related to an increased risk of intensive types such as steroid-dependent patients.     

郑州地区汉族糖尿病合并冠心病患者脂蛋白脂酶多态性

目的探讨脂蛋白脂酶(LPL)在2型糖尿病和糖尿病合并冠心病发病中的作用机制。方法测定糖尿病和糖尿病合并冠心病患者外周血白细胞LPL内含子6的PvuⅡ和内含子8的HindⅢ多态性,以及血清中甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-c)等的水平。结果糖尿病及糖尿病合并冠心病患者外周血LPL基因PvuⅡ和HindⅢ的等位基因P、H频率与对照组相比较无显著性差异。糖尿病和糖尿病合并冠心病患者LPL基因PvuⅡ多态性中的P ／P 基因型患者的TG、TC和LDL-c水平高于非P ／P 患者和对照组,HDL—c水平低于非P ／P 患者和对照组。结论LPL基因PvuⅡ突变位点与糖尿病合并冠心病患者体内脂质代谢紊乱有关,可通过了解LPL基因多态性以了解糖尿病和糖尿病合并冠心病脂质代谢紊乱的状况。     

Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis

BACKGROUND AND AIMS: Elicitation of an innate immune response to bacterial products is mediated through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs) and the NODs. The recently characterised Asp299Gly polymorphism in the lipopolysaccharide (LPS) receptor TLR4 is associated with impaired LPS signalling and increased susceptibility to Gram negative infections. We sought to determine whether this polymorphism was associated with Crohn's disease (CD) and/or ulcerative colitis (UC). METHODS: Allele frequencies of the TLR4 Asp299Gly polymorphism and the three NOD2/CARD15 polymorphisms (Arg702Trp, Gly908Arg, and Leu1007fsinsC) were assessed in two independent cohorts of CD patients (cohort 1, n = 334; cohort 2, n = 114), in 163 UC patients, and in 140 controls. A transmission disequilibrium test (TDT) was then performed on 318 inflammatory bowel disease (IBD) trios. RESULTS: The allele frequency of the TLR4 Asp299Gly polymorphism was significantly higher in CD (cohort 1: 11% v 5%, odds ratio (OR) 2.31 (95% confidence interval (CI) 1.28-4.17), p = 0.004; and cohort 2: 12% v 5%, OR 2.45 (95% CI 1.24-4.81), p = 0.007) and UC patients (10% v 5%, OR 2.05 (95% CI 1.07-3.93), p = 0.027) compared with the control population. A TDT on 318 IBD trios demonstrated preferential transmission of the TLR4 Asp299Gly polymorphism from heterozygous parents to affected children (T/U: 68/34, p = 0.01). Carrying polymorphisms in both TLR4 and NOD2 was associated with a genotype relative risk (RR) of 4.7 compared with a RR of 2.6 and 2.5 for TLR4 and NOD2 variants separately. CONCLUSION: We have reported on a novel association of the TLR4 Asp299Gly polymorphism with both CD and UC. This finding further supports the genetic influence of PRRs in triggering IBD.     

hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer

AIM: To determine the association of hOGG1 (8-oxoguanine glycosylase I, OGG1) polymorphism of Ser326Cys substitution with colon cancer risk and possible interaction with known environmental risk factors. METHODS: A case-control study with 125 colon cancer cases and 247 controls was conducted. RESULTS: There was no major difference in Ser326Cys genotype distribution between cases and controls. The meat intake tended to increase the odds ratio for colon cancer with an OR of 1.72 (95 % confidence interval; CI=1.12-2.76). Such tendency was more prominent in Cys/Cys carriers (OR=4.31, 95 % CI=1.64-11.48), but meat intake was not a significant risk factor for colon cancer in Ser/Ser or Ser/Cys carriers. The OR for colon cancer was elevated with marginal significance in smokers who were Cys/Cys carriers (OR=2.75, 95 % CI=1.07-7.53) but not in Ser/Ser or Ser/Cys carriers. CONCLUSION: These results suggest that the hOGG1 Ser326Cys polymorphism is probably not a major contributor to individual colon cancer susceptibility overall, but the Cys/Cys genotype may alter the impact of some environmental factors on colon cancer development.     

The influence of lipoprotein lipase gene variation on postprandial lipoprotein metabolism

Lipoprotein lipase (LPL) is one of the key enzymes in the metabolism of triacylglycerol-rich lipoproteins (TRL). We evaluated whether the association of LPL HindIII (H1/H2) and Serine447-Stop (S447X) polymorphisms may explain the interindividual variability observed during postprandial lipemia. Fifty-one healthy male volunteers (26 with the H2S447 genotype, 15 with the H1X447 genotype, and 10 with the H1S447 genotype) were subjected to a vitamin A-fat load test consisting of 1 g fat/kg body weight and 60,000 IU vitamin A. Blood was drawn every hour until the 6th hour and every 2 h and 30 min until the 11th hour. Data revealed that subjects that are homozygous for the H2 allele (H2H2) showed a higher postprandial response for small TRL, retinyl palmitate (RP), large TRL-RP, large TRL-B48, and small TRL-B48 levels. Furthermore, in the case of the S447X polymorphism, 447Ter carriers had a lower postprandial response for small TRL-RP, large TRL-B48, and small TRL-RP. Subjects with the LPL H2S447 genotype had higher plasma triacylglycerol, large TRL-triacylglycerol, large TRL-RP, small TRL-RP, and large TRL-B48 (P < 0.037) than H1X447 subjects. The modifications observed in postprandial lipoprotein metabolism in young normolipemic males with LPL polymorphism could be involved in the lower risk of coronary artery disease associated with the H1X447 genotype.     

Human NAD(P)H:quinone oxidoreductase 1 (NQO1) and sulfotransferase 1A1 (SULT1A1) polymorphisms and urothelial cancer risk in Taiwan

Purpose To investigate whether the NAD(P)H:quinone oxidoreductase 1 (NQO1) and sulfotransferase 1A1 (SULT1A1) polymorphisms are associated with urothelial cancer (UC) risk in Taiwan. Methods In this study, 600 study subjects (including 300 UC patients and 300 cancer-free controls) were recruited from September 1998 to December 2005. We analyzed the NQO1 and SULT1A1 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A comprehensive interview was conducted to collect information, including baseline characteristics and cigarette smoking status. We used an unconditional multivariate logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI). Results We found a significantly increased UC risk in study subjects with the NQO1 C/T and T/T genotypes (OR = 1.5; 95% CI: 1.03–2.1). A significantly increased UC risk was found in those with the SULT1A1 G/G genotype (OR = 2.0; 95% CI: 1.3–3.2). Subjects who had ever smoked with either the NQO1 C/T and T/T genotypes or the SULT1A1 G/G genotype had significantly increased UC risks, showing ORs of 3.0 and 5.3, respectively. Subjects carrying both the NQO1 C/T and T/T genotypes and the SULT1A1 G/G genotype had a significantly increased UC risk (OR = 3.7; 95% CI, 1.4–9.7). Moreover, those who had ever smoked with both the NQO1 C/T and T/T genotypes and the SULT1A1 G/G genotype had the highest UC risk (OR = 8.6; 95% CI: 2.5–29.7). Conclusions These findings suggest that NQO1 and SULT1A1 polymorphisms are associated with the risk of UC, particularly among those who have ever smoked.     

急性心肌梗死患者脂蛋白脂肪酶基因Ser447Stop的多态性研究

目的 探讨中国人群中脂蛋白脂肪酶基因Ser447Stop多态性与急性心肌梗死的相关性.方法 应用PCR和限制性片段长度多态性分析的方法测定86例急性心肌梗死患者和90例对照组脂蛋白脂肪酶基因Ser447Stop多态性.结果 急性心肌梗死组的CG GG基因型频率显著低于对照组(分别为0.174和0.422,P<0.05).急性心肌梗死组的G等位基因频率为0.087,亦显著低于对照组的0.217.急性心肌梗死亚组间的分析显示,血脂异常组CG GG基因型与G等位基因频率均显著低于血脂正常组(P<0.05).结论 脂蛋白脂肪酶基因Ser447Stop多态性与急性心肌梗死有一定的相关性,G等位基因可能是急性心肌梗死的一个保护性因素.     

细胞毒T淋巴细胞相关抗原4基因多态性与溃疡性结肠炎

目的炎症性肠病的发病与T细胞过度活化有关,细胞毒T淋巴细胞相关抗原4（CTLA-4）是重要的T细胞活化负性调节因子.本课题研究CTLA-4基因启动子区-1722位点（T/C）及-1661位点（A/G）多态性与中国汉族人群中溃疡性结肠炎（UC）的相关性.方法采用PCR-限制性片段长度多态性方法,对87例中国汉族UC患者和116例正常对照者进行CTLA-4基因-1722位点和-1661位点多态性检测.结果UC患者CTLA-4基因-1661位点A/G＋G/G基因型频率,-1661位点G等位基因频率显著高于正常对照组（34.5%比15.5%,P=0.002,OR=2.865,95%CI=1.467～5.596;19.0%比8.2%,P=0.002,OR=2.624,95%CI=1.435～4.796）;而在-1722位点的基因型频率、等位基因频率与对照组比较差异无统计学意义（P＞0.05）.结论CTLA-4基因启动子区-1661位点G等位基因与中国汉族UC存在显著相关性.     

Potentially protective effects of the Ser447-Ter mutation of the lipoprotein lipase gene against the development of coronary artery disease in Japanese subjects via a beneficial lipid profile

Several DNA variants at the lipoprotein lipase (LPL) gene locus have been found to be associated with the plasma lipid levels and the prevalence of coronary artery disease (CAD). In particular, the Ser447-termination (Ter) mutation at the exon 9 of the LPL gene has the potential to elevate the plasma high-density lipoprotein (HDL) levels, but it remains unknown in the Japanese population. The present study investigated 93 CAD patients and 96 age- and sex-matched healthy controls. The Ser447-Ter mutation was determined by polymerase chain reaction restriction fragment length polymorphism method. The allelic frequency of the Ser447-Ter mutation was 0.103 in all subjects. The Ser447-Ter (GG and CG) group was associated with significantly higher levels of plasma HDL-cholesterol (p<0.001) and lower levels of plasma triglyceride than the CC group (p<0.02). The peak particle size of low-density lipoprotein (LDL) was significantly larger in the Ser447-Ter (GG and CG) group than in CC group (p<0.05). The frequency of the Ser447-Ter genotype in GG and CG was significantly lower in CAD than in the controls (11.9% vs 26%, odds ratio = 0.38; 95% confidence interval, 0.18-0.81; p<0.02). These results suggest that the Ser447-Ter mutation of the LPL gene is associated with high plasma HDL-cholesterol levels, low plasma triglyceride levels and a larger LDL particle size. This mutation may have a protective effect against the development of CAD via its favorable lipoprotein profile.