解偶联蛋白3基因启动子区-55(C>T)多态与中国人静息能量消耗及体脂含量与分布的关系

目的研究解偶联蛋白3基因(UCP3)启动子区-55(C>T)多态与中国人静息能量消耗、体脂参数的关系。方法在300名中国人(正常体重91人,超重/肥胖209人)中,用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restrictionfragment length polymorphisms ,PCR-RFLP)检测UCP3基因启动子区-55(C>T)变异,并测定其静息能量消耗、体脂含量及分布。结果UCP3基因启动子区-55(C>T)多态基因型频率与肥胖及肥胖类型均无相关。正常体重组TT基因型者静息能量消耗水平显著高于CT及CC基因型者(P<0·05) ;超重/肥胖组各基因型者间比较亦有同样趋势。在超重/肥胖组,TT基因型者FM/FFM值与CT及CC基因型者差异有显著意义(P<0·01)。结论UCP3基因启动子区-55(C>T)多态与中国人静息能量消耗相关,该变异可能通过对静息能量消耗的影响调节机体的能量代谢。     

解偶联蛋白3基因 -55 C→T变异与中国人体脂代谢、含量、分布及2型糖尿病的关系

目的 研究解偶联蛋白3（uncoupling protein 3,UCP3）基因－55C→T变异与中国人体脂含量、体脂代谢、体脂分布及2型糖尿病的关系。方法 用聚合酶链反应－限制性片段长度多态性检测了165名糖耐量正常者（男／女为69／96）及151例2型糖尿病患者（男／女为62／89）UCP3基因－55C→T变异的基因型，核磁共振8检测局部体脂含量，酶法及硫酸葡聚糖－锰沉淀法测血总胆固醇及血高密度脂蛋白胆固醇，并用公工密度脂蛋白胆固醇。结果 （1）非糖尿病中国人与白种人比较等位基因频率及基因型频率差异均无显著性（P分别为0.1120和0.0646），与Pima印地安人比较差异均有显著性（P分别为0.0105及0.0314）。（2）逐步回归分析发现，UCP3基因－55C→T变异的独立相关变量：糖耐量正常男性组为血高密度脂蛋白胆固醇及低密度脂蛋白胆固醇，糖耐量正常女性组为股部脂肪面积，2型糖尿病男性组为血甘油三酯，2型糖尿病妇性组为腰臀比。（3）2型糖尿病组与糖耐量正常组相比，等位基因频率的差异有显著性（P为0.0358）。携带T等位基因发生2型糖尿病的相对风险的比数比为1.434（95％可信区间为1.031-1.995）。结论 UCP3基因－55C→T变异与中国人局部体脂含量、体脂代谢及分布相关，但存在性别及疾病状态的差异。该变异与中国人2型糖尿病的发生相关。     

载脂蛋白AⅠ基因启动子和内含子1中的单核苷酸多态性对其表达的影响

目的构建含ApoAⅠ基因调控区和荧光素酶报告基因的真核表达载体，探讨ApoAⅠ基因启动子区域-75bp G→A置换及第1内含子＋83bp C→T置换对ApoAⅠ表达的影响。方法采用PCR方法扩增人染色体中含ApoAⅠ基因-145～＋289bp的DNA片段，筛选出含ApoAⅠAA／CC基因型（-75bp变异，＋83bp无变异）、GG／TT基因型（-75bp无变异，＋83bp变异）及GG／CC（-75bp和＋83bp均无变异）的DNA片段，构建含以上3个基因片段的pUC重组载体，经SacⅠ和BglⅡ酶切后，再将不同的DNA片段连接到含荧光素酶报告基因的pGL2载体中，获得多个重组克隆。采用阳离子脂质体转染法将携带萤火虫荧光素酶报告基因的重组质粒和携带海肾荧光素酶报告基因的对照质粒共转染HepG2细胞，经48h培养，用化学发光法测定细胞裂解液中荧光素酶的活性，以反映ApoAⅠ的表达水平。结果质粒重组获得3个pGL2-ApoAⅠ-L（-2500～＋289bp）长片段质粒和3个pGL2-ApoAⅠ-S（-145～＋289bp）短片段质粒，分别含AA／CC、GG／TT及GG／CC3种基因型。荧光素酶报告基因活性显示：ApoAⅠAA／CC或GG／TT基因型携带者引起荧光素酶相对活性明显低于GG／CC基因型者。结论基因启动子ApoAⅠ-75bp G→A置换和＋83bp C→T置换对ApoAⅠ转录活性起抑制作用，这可能是-75A和＋83T等位基因携带者高密度脂蛋白血浆水平降低的原因。     

湖北汉族人群TIM-3基因多态性与变应性哮喘的相关性

目的分析湖北地区汉族人群T细胞免疫球蛋白域粘蛋白域蛋白-3（T cell simmunoglobulin domain and mucin domain protein-3，TIM-3）启动子区-1541C／T和-574G／T单核苷酸多态性，探讨其与支气管哮喘易感性之间的关系。方法分别采用聚合酶链反应-限制性片段长度多态性和等位基因特异性聚合酶链反应检测湖北地区153例哮喘患者和130名健康者TIM-3启动子区-1541C／T和-574G／T的单核苷酸多态性，计算基因型和等位基因频率。结果（1）湖北地区健康人群TIM-3启动子区-1541位CC、CT和TT基因型频率分别是0．961、0．039和0，而哮喘人群其频率分别为0．935、0．065、0，其基因型和等位基因频率均与对照组差异无统计学意义（P=0．314，P=0．321）；（2）湖北地区健康人群TIM-3启动子区-574位GG、GT和TT基因型频率分别是0．992、0．008和0，而哮喘人群频率分别为0．941、0．059、0，其基因型和等位基因频率均与对照组差异有统计学意义（P=0．046，P=0．048）。结论湖北汉族人群TIM-3启动子区存在多态性变异，其中-574G／T单核苷酸多态性可能与湖北地区汉族成人变应性哮喘易感性有关。     

基质金属蛋白酶-2和-9基因多态性与结直肠癌的相关性

目的探讨基质金属蛋白酶（matrix metalloproteinase，MMP）-2和-9基因启动子区多态性与结直肠癌的关系。方法应用变性高效液相色谱法和限制性片段长度多态性分析方法分别检测126例结直肠癌患者和126名正常对照者的MMP-2—1306C/T和MMP-9—1562C／T多态性，分析其基因型与结直肠癌发病风险及临床病理参数的相关性。结果MMP-2—1306C／C基因型频率在结直肠癌组中显著高于对照组（P〈0．05），与CT＋TT基因型携带者比较，CC基因型携带者患结直肠癌的风险约增加2倍（OR：1．959；95％CI：1．055～3．637）。而且在结直肠癌中，MMP-2—1306C／T多态性与肿瘤的浸润深度之间差异有统计学意义（P〈0．05），CC基因型的肿瘤更容易浸润到外膜。MMP-9—1562C／T多态性的基因型及等位基因频率在结直肠癌组和对照组间的分布差异无统计学意义（P〉0．05）。结论MMP-2—1306C／T多态性可能与中国人群结直肠癌的遗传易感性相关，且CC基因型的肿瘤更易浸润到外膜。     

RET基因功能性单核苷酸多态与先天性巨结肠风险

目的先天性巨结肠是一种肠神经系统发育异常导致的先天性消化道畸形。RET基因是其主要致病基因，本研究探讨RET启动子区的两个功能性单核苷酸多态-5G／A和-1A／C与先天性巨结肠遗传易感性的关系。方法以聚合酶链反应（PCR）和直接测序（direct-squencing）分析方法，检测了52例先天性巨结肠病人和120例正常对照者RET-5G／A和-1A／C的基因型。比较不同基因型与先天性巨结肠风险的相关性。结果RET-5AA和-1CC基因型频率在先天性巨结肠患者和正常对照中的分布有显著性差异（P值分别为〈0．001和0．003），携带RET-5AA和-1CC基因型者罹患先天性巨结肠的风险分别是携带RET-5GG和-1AA基因型者的11．40倍（95％CI，2．89-53．09）和4．65倍（95％CI，0．98-32．30）。此外，单倍型分析发现，同时携带两种风险等位基因的A-C单倍型者的患病风险比携带G-A型者增高了4．38倍（95％CI，2．53-11．90）。结论RET基因功能性单核苷酸多态-5G／A和-1A／C多态可能是中国人先天性巨结肠的遗传易感因素。     

汉族人群一氧化氮合酶基因三个位点单核苷酸多态性与静息心率相关性研究

目的研究汉族人群的一氧化氮合酶（nitric oxide synthase，NOS）基因NOS3-922A／G和NOS3 894G／T以及NOS2-1173C／T3个位点的单核苷酸多态性（single nucleotide polymorphisms，SNP）与静息心率的相关性。方法随机选择自然人群个体211名为研究对象，获取其静脉血白细胞基因组DNA。用等位基因特异性引物PCR技术检测NOS3-922A／G、NOS3 894G／T、NOS2-1173C／T的SNP。结果NOS3-922A／G的AA、AG、GG，NOS3 894G／T的GG、GT和TT与NOS2-1173C／T的CC、CT和TT各基因型频率分布，均符合Hardy-Weinberg平衡（P〉0．05）。NOS3-922A／G各等位基因AA、AG、GG静息心率比较，发现携带从等位基因者静息心率较GG者高，差异有统计学意义（P〈0．01）。NOS3 894G／T各等位基因静息心率比较，发现携带GG等位基因者静息心率较TT者高，差异有统计学意义（P〈0．05）。NOS2-1173C／T各等位基因的静息心率比较，差异均无统计学意义（P〉0．05）。结论NOS3-922A／G与NOS3 894G／TSNP突变型其静息心率较野生型降低，提示上述位点SNP可能与其静息心率有相关性。     

汉族人白细胞介素-18基因启动子多态性与慢性乙型肝炎的相关性研究

目的 探讨中国汉族人白细胞介素-18（interleukin-18,IL-18）基因启动子单核苷酸多态性及其与慢性乙型肝炎易感性之间的关系。方法 应用序列特异性引物一聚合酶链反应技术，检测231例慢性乙型肝炎患者和300名正常人儿．馏基因启动子-607C/A、-137G／C单核苷酸多态性位点基因型。结果 正常对照组和慢性乙型肝炎组中，IL-18基因启动子-607C/A位点3种基因型频率分别为CC型：0．22（66／300）和0．27（62／231），CA型：0．53（160／300）和0．50（116／231），AA型：0．25（74／300）和0．23（53／231）；IL-18基因启动子-137G／C位点3种基因型频率分别为GG型：0．67（202／300）和0．79（182／231），GC型：0．30（90／300）和0．19（45／231），CC型：0．03（8／300）和0．02（4／231）。经Y0检验，慢性乙型肝炎组IL-18基因启动子-137GG分布频率显著高于正常对照组（X^2=8．55，P=0．003），而-607C／-137C和-607A／-137C单倍型频率显著低于正常对照组。进一步比较慢性乙型肝炎患者儿．馏基因启动子多态性与乙型肝炎病毒（hepatitis Bvirus，HBV）DNA复制的关系，发现高水平HBV—DNA组-607位点AA基因型分布频率明显低于低水平HBV—DNA组（Y2=6．03，P=0．014）。结论 汉族人慢性乙型肝炎与IL-18基因启动子-607C/A、-137G／C单核苷酸多态性相关，其中IL-18基因启动子-137位点C等位基因可能对机体HBV感染有保护作用，而启动子-607位点AA型对感染后HBV—DNA的复制可能有抑制作用。     

纤维蛋白原β基因-148C/T多态性与脑梗死的关系

目的探讨纤维蛋白原（fibrinogen，Fg）β基因启动子区-148C／T多态性、血浆Fg水平与急性动脉粥样硬化性脑梗死的关系。方法用多聚酶链反应．限制性片段长度多态性方法对151例脑梗死患者和101名健康对照进行Fgβ-148C／T基因多态性分析，并应用凝血酶原时间衍生法检测血浆Fg水平。结果脑梗死组血浆Fg水平明显高于对照组（P〈0．01）；T等位基因携带者较CC基因型者血浆Fg水平明显增高（P〈0．01）；按性别分组后差异仍有统计学意义；按年龄段分组后，病例组各组T等位基因携带者较CC基因型者血浆Fg水平增高（P〈0．05）。中年梗死组较中年对照组T等位基因频率的差异有统计学意义（P〈0．05）。结论Fgβ-148C／T基因多态性影响血浆Fg水平，T等位基因可能独立或通过与其它血栓危险因素或环境因素协同作用增高血浆Fg水平，成为脑动脉血栓形成的危险因素。     

IL-10-592A〉C多态与宫颈癌遗传易感的相关性分析

目的研究白细胞介素10（IL—10）基因启动子区-592A〉C单核苷酸多态性（SNP）与广东汉族妇女宫颈癌易感的关系。方法利用聚合酶链式反应-限制性片段长度多态性（PCR—RFLP）分析技术,对70例宫颈癌患者和108名健康对照个体的IL-10—592A〉C多态住点进行分型,比较各组间等位基因及基因型频率的分布,分析该多态位点与宫颈癌易感的相关性。结果AA、AC、CC基因型在病例组中的频率分别为50．0％、32．9％和17．1％,在对照组中分别是47．3％、40．7％和12．0％,两组间基因型频率分布差异无统计学意义（Х^2=1．56,P=0．459）;以AA基因型作为参照,AC和CC基因型均没有显著增加个体患宫颈癌的风险（OR=0．76,95％CI=0．39-1．48,P=0．421以及OR=1．35,95％CI：0．55—3．29。P=0．516）。结论IL—10基因基因启动子区-592A〉C多态位点与广东汉族妇女人群宫颈癌的易感性无关。     

Resting energy expenditure and body composition in rural Sarawaki adults

The resting energy expenditure (REE) of 43 men and 41 nonpregnant women aged 18–42, of the Iban tribe in rural Sarawak, was measured using the Oxylog and analyzed in relation to fat mass (FM) and fat-free mass (FFM) derived from measurements of skinfold thickness, to estimates of the specific energy expenditure of the FFM, and to microclimatic variables. Measured REEs exceeded values predicted from FFM by 9–22%, but were consistent with the metabolic rates expected of Western adolescents of comparable body size and composition. In both sexes, body fat content significantly influenced REE after accounting for nonlinear effects of variation in FFM. This is consistent with reported high adipocyte metabolic rates in obese Westerners, and with the hypothesis that Iban may possess a relatively large capacity for fat mobilization and storage. Therefore, in some populations, terms representing both FM and FFM should be included in equations describing REE. These findings are consistent with postulated evolutionary advantages of efficiency in regulation of energy turnover. © 1993 Wiley-Liss, Inc.     

Visceral obesity attenuates the effect of the hepatic lipase -514C>T polymorphism on plasma HDL-cholesterol levels in French-Canadian men

The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride (TG) levels, low HDL-cholesterol concentrations and alterations in LDL composition and concentration. A functional, non-coding -514C>T single nucleotide polymorphism (SNP) of the hepatic lipase gene (LIPC) has been related to variation in HDL-cholesterol concentrations. OBJECTIVES: To investigate the hypotheses that the LIPC -514C>T polymorphism may be associated with a deteriorated lipoprotein-lipid profile and that environmental factor, such as abdominal obesity, alters this association. METHODS: A total of 235 French-Canadian men from the greater Quebec City area were assigned into three groups on the basis of their LIPC -514C>T SNP, including 149 CC homozygotes, 75 CT heterozygotes, and 11 TT homozygotes. RESULTS: In the present study, the highest values of BMI, waist circumference, and accumulation of visceral adipose tissue (VAT) were observed among TT homozygotes (p<0.05). After adjustment for age and BMI, TT homozygotes still showed higher plasma apolipoprotein (apo) AI and HDL-TG concentrations than the two other groups (p<0.05). When the two genotype groups (CC vs CT/TT) were further divided on the basis of VAT accumulation using a cut-off point of 130 cm(2) (high vs low) it appears that irrespective of the genotype subjects with low VAT had higher HDL(2)-cholesterol concentrations (p<0.0001). However, lean carriers of the T allele had higher plasma HDL(2)-cholesterol levels than lean CC homozygotes. The beneficial effect of the T allele on plasma HDL(2)-cholesterol levels was abolished in the presence of visceral obesity (VAT>130 cm(2)).CONCLUSION: In summary, the presence of visceral obesity attenuates the impact of the LIPC -514C>T polymorphism on plasma HDL(2)-cholesterol levels.     

<Emphasis Type="Italic">APOA5</Emphasis> gene variation modulates the effects of dietary fat intake on body mass index and obesity risk in the Framingham Heart Study

Diet is an important environmental factor interacting with our genes to modulate the likelihood of developing lipid disorders and, consequently, cardiovascular disease risk. Our objective was to study whether dietary intake modulates the association between APOA5 gene variation and body weight in a large population-based study. Specifically, we have examined the interaction between the APOA5-1131T>C and 56C>G (S19W) polymorphisms and the macronutrient intake (total fat, carbohydrate, and protein) in their relation to the body mass index (BMI) and obesity risk in 1,073 men and 1,207 women participating in the Framingham Offspring Study. We found a consistent and statistically significant interaction between the -1131T>C single-nucleotide polymorphism (SNP; but not the 56C>G) and total fat intake for BMI. This interaction was dose-dependent, and no statistically significant heterogeneity by gender was detected. In subjects homozygous for the -1131T major allele, BMI increased as total fat intake increased. Conversely, this increase was not present in carriers of the -1131C minor allele. Accordingly, we found significant interactions in determining obesity and overweight risks. APOA5-1131C minor allele carriers had a lower obesity risk (OR, 0.61, 95%; CI, 0.39-0.98; P = 0.032) and overweight risk (OR, 0.63, 95%; CI, 0.41-0.96; P = 0.031) compared with TT subjects in the high fat intake group (>or=30% of energy ) but not when fat intake was low (OR, 1.16, 95%; CI, 0.77-1.74; P = 0.47 and OR = 1.15, 95%; CI, 0.77-1.71; P = 0.48) for obesity and overweight, respectively). When specific fatty acid groups were analyzed, monounsaturated fatty acids showed the highest statistical significance for these interactions. In conclusion, the APOA5-1131T>C SNP, which is present in approximately 13% of this population, modulates the effect of fat intake on BMI and obesity risk in both men and women.     

Relationships between physical activity, physical fitness, muscle strength and nutritional state in 5- to 11-year-old children

The purpose of the present study was to assess different aspects of physical activity and fitness in order to develop a basis for sport programmes for overweight and obese children. Eighty-eight prepubertal children (49 boys, 39 girls, 4.8–11.4 years old, 61% obese, 14% overweight and 25% normal weight) were examined. Body composition was assessed by combined use of anthropometrics and bioelectrical impedance analysis. Resting energy expenditure (REE) and total energy expenditure (TEE) were measured by indirect calorimetry (IC) and individually calibrated 24-h heart rate (HR) monitoring, respectively. Activity-related energy expenditure (AEE) and physical activity level (PAL) were calculated from TEE and REE. Fitness [assessed by O₂-pulse, respiratory exchange ratio (RER) at submaximal work intensities] was determined by ergometry. The maximal isometric muscle strength of the legs (m. quadriceps, Fa max, m. ischiocruralis, Fb max) was measured by computer tensiometry. Children were grouped according to their nutritional state, AEE, O₂-pulse and muscle strength. When compared with normal weight children, obese and overweight children had increased fat mass (FM), fat-free mass (FFM), waist-to-hip ratio and REE, but no group differences were observed for TEE, AEE, and PAL. Obese and overweight children spent more hours per day watching TV. After correction for body weight and FFM, no group differences in REE were observed, but normal weight children had a higher O₂-pulse than overweight and obese children. By contrast, RER was increased in the latter group. The fittest group had the lowest body weight, BMI, FM and FFM. Children with a low O₂-pulse spent more hours per day watching TV. Grouping children according to their degree of muscle strength, younger children (4–7.5 years) did not show group differences in nutritional state, energy expenditure, physical activity and fitness. However, in the group of 7.6- to 11-year-old children, those with the greatest muscle strength and FFM had reduced BMI, skin folds, FM and FFM. FM correlated inversely with O₂-pulse, but was not associated with TEE, AEE, PAL or muscle strength. By contrast TV consumption was positively associated with FM. To summarize, overweight and obese children were less fit and watched more TV than their normal weight counterparts. FM did not correspond to TEE, AEE or PAL. Muscle strength was not associated with FM in young children, but was inversely associated with FM in older children. Our cross-sectional data are consistent with the idea that increased fitness and reduced physical inactivity may prevent children from being overweight. Accepted: 18 February 2000     

Changes in regional body composition explain increases in energy expenditure in elite junior basketball players over the season

We aimed to analyze the association between changes in total and regional fat (FM) and fat-free mass (FFM) over a season with resting (REE) and total energy expenditure (TEE) in elite basketball players. At the beginning of the pre-season and at the final of the competitive period, measures of total and regional FM, FFM, lean soft tissue (LST), and bone mineral estimated by DXA and REE by indirect calorimetry were obtained in eight males and nine females of the Portuguese basketball team (16-17 years). TEE was assessed by doubly labeled water. Handgrip and a vertical-jumping were used to assess strength and power. Changes were expressed as a percentage from the baseline values. Resting energy expenditure and TEE increased by 13.2 ± 12.6 and 13.3 ± 12.7% (p < 0.01), respectively. Increases in FFM (3.6 ± 2.2%) and reductions in relative FM (-4.0 ± 6.6%) were observed (p < 0.01). The strength and power increased by 14.4 ± 9.9 and 9.8 ± 10.6%, respectively (p < 0.001). Alone, FFM and arms LST differences explained 25 and 23% of the total variance in REE alteration. These variables remained associated after adjusting for gender and baseline values (β = 0.536, p = 0.042; and β = 2.023, p = 0.016, respectively). Over the season, the REE increase was explained by changes in FFM. The increase in REE along with the strength and power improvement may suggest that a qualitative change in the metabolic active tissues occurred. Furthermore, these findings highlight the regional LST contribution, specifically located at the upper limbs, as a key component for the higher REE occurred over the season in junior basketball players.     

Investigation of 3111T/C polymorphism of the CLOCK gene in obese individuals with or without binge eating disorder: association with higher body mass index

Loss of circadian patterning of metabolism-related functions seems to play a role in the pathogenesis of obesity; therefore, it is reasonable to hypothesize that the functional 3111T/C single nucleotide polymorphism (SNP) of the (Circadian locomotor output cycles kaput) CLOCK gene may have a part in the genetic susceptibility to obesity. The aim of this study was to assess the frequencies of 3111T/C CLOCK gene SNP in overweight/obese subjects with or without binge eating disorder (BED) as compared to normal weight healthy controls. A total of 284 Caucasian subjects, including 92 normal weight healthy subjects and 192 overweight/obese patients (107 with BED) participated into the study. Genotype and allele frequencies did not significantly differ between normal weight controls and overweight/obese patients with and/or without BED. However, overweight/obese patients carrying the CC genotype had significantly higher values of body mass index (BMI) as compared to those carrying the CT and/or TT genotypes. Moreover, obese class III individuals had a significantly higher frequency of both the CC genotype and the C allele as compared to individuals with BMI<40 kg/m(2). Present findings show for the first time that the 3111T/C SNP of the CLOCK gene is not associated to human obesity and/or BED, but it seems to predispose obese individuals to a higher BMI.     

β3-肾上腺素能受体基因及解偶联蛋白2基因复合变异与中国人肥胖症的关系

目的　探讨 β3-肾上腺素能受体 ( β3- adrenergic receptor,ADRβ3)基因 Trp6 4 Arg和解偶联蛋白 2 ( uncoupling protein 2 ,UCP2 )基因 Ala5 5 Val复合变异对中国汉族人群肥胖症发生的影响。方法　采用聚合酶链反应 -限制性片段长度多态性 ( PCR- RFL P)技术 ,对 ADRβ3基因 Trp6 4 Arg和 UCP2基因Ala5 5 Val变异进行检测。 119例肥胖症患者 ,平均体重指数 ( body mass index,BMI)为 ( 2 7.9± 2 .98) kg/m2 ,177名正常对照组 ,平均 BMI为 ( 2 1.9± 1.9) kg/ m2 。结果　 ( 1)肥胖患者的 ADRβ3基因 Trp6 4 Arg突变携带者的频率与正常对照组的差异无显著性 ( P>0 .0 5 ) ;正常人携带 Trp6 4 Arg基因变异者有较高的空腹和口服葡萄糖耐量试验 ( oral glucose tolerance test,OGTT) 2小时血糖水平。 ( 2 )肥胖患者携带 UCP2基因 Ala5 5 Val纯合子变异的基因频率明显高于正常对照组的 ( OR=3.71,P=0 .0 0 1) ;正常人携带 Ala5 5 Val基因变异者有较高的 BMI水平。 ( 3)单一的 UCP2或 ADRβ3基因变异时 ,肥胖组的变异基因频率与正常人的分布差异无显著性 ( P>0 .0 5 ) ;但 UCP2和ADRβ3两基因同时发生变异时 ,肥胖组的变异基因频率则明显高于正常组 ( OR=2 .5 7,P=0 .0 0 9)。 ( 4 )携带 Val/ Val Trp/ A     

Investigation of 3111T/C polymorphism of the CLOCK gene in obese individuals with or without binge eating disorder: Association with higher body mass index

Loss of circadian patterning of metabolism-related functions seems to play a role in the pathogenesis of obesity; therefore, it is reasonable to hypothesize that the functional 3111T/C single nucleotide polymorphism (SNP) of the (Circadian locomotor output cycles kaput) CLOCK gene may have a part in the genetic susceptibility to obesity. The aim of this study was to assess the frequencies of 3111T/C CLOCK gene SNP in overweight/obese subjects with or without binge eating disorder (BED) as compared to normal weight healthy controls. A total of 284 Caucasian subjects, including 92 normal weight healthy subjects and 192 overweight/obese patients (107 with BED) participated into the study. Genotype and allele frequencies did not significantly differ between normal weight controls and overweight/obese patients with and/or without BED. However, overweight/obese patients carrying the CC genotype had significantly higher values of body mass index (BMI) as compared to those carrying the CT and/or TT genotypes. Moreover, obese class III individuals had a significantly higher frequency of both the CC genotype and the C allele as compared to individuals with BMI < 40 kg/m². Present findings show for the first time that the 3111T/C SNP of the CLOCK gene is not associated to human obesity and/or BED, but it seems to predispose obese individuals to a higher BMI.