重庆地区汉族老年人群klotho G-395A、F352V与C370S基因多态性及其组合分布

目的 研究重庆地区汉族老年人群klotho G-395A、F352V与C370S 3个位点的单核苷酸多态性(SNP)及其等位基因频率、单倍型组合分布特征.方法 利用单一等位基因特异性引物PCR技术检测klotho G-395A、F352V、C370S的SNP,应用聚类分析其基因多态性特征.结果 klotho G-395A SNP 基因型分布 GG、GA、AA分别为47.66%、42.58%、9.76%,G、A等位基因频率分别为68.95%、31.05%;klotho F352V SNP 基因型分布 FF、FV、VV分别为35.49%、59.09%、5.61%,F、V等位基因频率分别为65.04%、34.96%;klotho C370S SNP 基因型分布CC CS、SS分别为37.30%、58.76%、3.88%,C、S等位基因频率分别为66.68%、33.32%.研究发现了klotho基因在3个位点的SNP前10种组合基因型分布:klotho G-395G+F352V+C370S 253例(16.92%),klotho G-395A+F352V+C370S 241例(16.12%),klotho G-395G+F352V+C370C 152例(10.17%),klotho G-395A+F352V+C370C 131例(8.76%),klotho G-395G+F352F+C370S 126例(8.43%),klotho G-395A+F352F+C370C 121例(8.09%),klotho G-395G+F352F+C370C 109例(7.29%),klotho G-395A+F352F+C370C 86例(5.75%),klotho A-395A+F352V+C370S 52例(3.48%),klotho A-395A+F352F+C370C 30例(2.01%),klotho G-395G+V352V+C370S 30例(2.01%).结论 本研究首次揭示了klotho基因的3个位点的SNP基因型组合分布特征,为进一步开展klotho基因及其表达研究提供了线索和依据.     

Klotho基因G-395A多态性与动脉硬化的相关性研究

目的研究重庆市汉族人群Klotho基因启动子区域G-395A单核苷酸多态性的分布,探讨该多态性位点与动脉硬化的相关性。方法232例健康体检者均进行臂踝脉搏波传导速度测定,并记录动脉硬化的传统危险因素,根据测定结果分为动脉硬化组(130例)和对照组(102例)。应用TaqMan探针等位基因特异性杂交分析法对Klotho基因G-395A多态性位点进行分析。结果G-395A多态性位点共检测出GG、GA、AA3种基因型,频率分别为60.3%、34.1%和5.6%,符合Hardy-Weinberg平衡。动脉硬化组-395A等位基因的频率显著低于对照组(33.1%vs48.0%,P=0.022)。logistic回归分析,调整传统危险因素后-395A与动脉硬化呈负相关(P=0.042,OR=0.537,95%CI:0.295~0.977)。结论Klotho基因-395A等位基因可能是动脉硬化的遗传学保护因素。     

Association of resistin gene 3'-untranslated region +62G-->A polymorphism with type 2 diabetes and hypertension in a Chinese population

Resistin, a recently discovered polypeptide, antagonizes insulin action and may play a part in the pathogenesis of insulin resistance. This study investigates whether resistin gene polymorphism can be associated with type 2 diabetes. We studied 1102 Chinese type 2 diabetes patients and 743 subjects without diabetes. The resistin 3'-untranslated region (UTR) +62G-->A polymorphism was determined by PCR. Type 2 diabetes subjects had a lower frequency of resistin gene 3'UTR +62A allele (GG:GA/AA, 83.5%:16.5%) than the controls (GG:GA/AA, 75.1%:24.9%; odds ratio, 1.524; 95% confidence interval, 1.268-1.831; P < 0.001). Unexpectedly, diabetic patients with the GG genotype had a higher prevalence of hypertension (GG:GA/AA, 49.8%:36.2%; odds ratio, 1.375; 95% confidence interval, 1.116-1.693; P = 0.001). Logistic regression analysis confirmed that the resistin gene 3'UTR +62G-->A polymorphism acts as an independent contributing factor to type 2 diabetes and hypertension. The mean systolic and diastolic blood pressure levels in diabetic subjects with the GG genotype (144 +/- 21/87 +/- 13 mm Hg) were significantly higher than those in subjects with GA/AA variants (139 +/- 21/84 +/- 14 mm Hg; P = 0.004 and P = 0.002, respectively). Multiple linear regression analysis showed resistin gene polymorphism to be an independent factor associated with systolic and diastolic blood pressures in type 2 diabetes patients. These findings suggest that resistin may play a role in the pathogenesis of type 2 diabetes and insulin resistance-related hypertension.     

Cognitive function among physically independent very old people in an urban Japanese community

Background:   A study was conducted to clarify the characteristics of cognitive function among physically independent very old people dwelling in an urban community in Japan.
Methods:   Five hundred and thirteen old-old (aged 75–84 years) and 168 oldest-old (aged 85–100 years) adults participated. We carried out the Mini-Mental State Examination (MMSE) for measuring cognitive functions in the elderly. Age-related differences in the total score and subscale scores of the MMSE were analyzed by sex using ancova , controlling for education, vision and hearing problems.
Results:   Mean MMSE scores for old-old and oldest-old men were 27.5 and 25.9, respectively, and those for old-old and oldest-old women were 27.8 and 25.0, respectively. Age-related differences in the MMSE total score between the old-old and oldest-old were observed in both sexes, suggesting that overall cognitive functions continue to decline over time in very old age. Age-related differences between the old-old and oldest-old in items measuring, registration, calculation and delayed recall were observed in both sexes, and also in those assessing time orientation, place orientation, delayed recognition, writing sentences, and copying figures were observed in women.
Conclusion:   These findings suggest that the faculties are those most sensitive to normal aging among very old individuals. There were no age group differences in five items: reverse spelling, naming objects, repeating a sentence, listening and obeying, and reading and obeying.     

抵抗素基因+299G/A多态性与T2DM并高血压病的相关性

目的研究抵抗素基因＋299G／A多态性与中国北方地区汉族人群2型糖尿病（T2DM）并高血压病的关系。方法采用聚合酶链式反应-限制性片段长度多态性技术检测北方地区汉族人群261例T2DM患者的抵抗素基因内含子2区299G／A突变。结果T2DM组GG、GA、AA基因型及G／A等位基因频率与非T2DM组比较有显著统计学差异（P〈0．01）；T2DM组GG基因型携带者空腹血糖明显高于AA基因型携带者（P〈0．05）。多元线性逐步回归分析显示，抵抗素基因＋299G／A与收缩压、舒张压无明显相关性。结论抵抗素基因＋299G／A多态性与T2DM有关．与高血压病元明显相关性。     

中老年患者KLOTHO基因G-395A多态性与心力衰竭和心肌纤维化的相关性

目的:观察分析中老年患者KLOTHO基因G-395A多态性与心力衰竭(HF)和心肌纤维化的相关性。方法:随机选择无血缘关系的中老年患者212例, 提取外周血白细胞基因组DNA, 采用单一等位基因特异性引物PCR技术检测KLOTHO基因G-395A位点多态性,分析其在不同年龄组的分布是否有统计学意义;并把中老年患者分为HF组和非HF组,分析KLOTHO基因G-395A多态性与HF的相关性及与HF各严重程度分级的相关性;同时采用ELISA方法检测上述212例患者血液标本血清中Ⅰ型前胶原羧基端肽（PⅠCP）,Ⅲ型前胶原氨基端肽（PⅢNP）的浓度,分析KLOTHO基因G-395A多态性与心肌纤维化的相关性。结果:①G-395A位点存在多态性,出现3种基因型。②该位点基因型在中老年患者中频率分布总体上没有显著差异（χ2=12.159 P=0.121）;进一步分析各年龄组两两之间与基因型频率分布均无显著差异。③中老年患者KLOTHO基因G-395A多态性与HF发病危险性呈显著相关（χ2=23.634 P=0.00）;进一步分析显示AG是GG易患HF的1.991倍;AA是GG易患HF的1.527倍;GG可能对HF是保护因素。而与HF分级差异比较没有统计学意义（P=0.202）。④Ⅰ、Ⅲ型胶原浓度及Ⅰ/Ⅲ比值与中老年患者G-395A的3种基因型比较没有显著差异,与基因型不相关。结论:在中老年患者中, KLOTHO基因启动子区G-395A呈现3种多态性,这3种多态性与HF发病危险性呈显著相关, 携带A等位基因发生HF的危险性明显高于携带G等位基因的患者,GG可能对HF是保护因素;而与HF分级差异比较及与心肌纤维化程度比较没有统计学意义。     

Association of tumor necrosis factor receptor 1 gene polymorphism with bone mineral density

Background:   Estrogen deficiency in postmenopausal women causes an increased production of proinflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α. These cytokines are associated with an increase of bone turnover and an acceleration of bone loss. Tumor necrosis factor-α is known to promote osteoclastogenesis via TNFR1, one of the tumor necrosis factor receptors (TNFR). Therefore, the purpose of the present report was to investigate the association of TNFR1 gene polymorphism with bone mineral density (BMD) in postmenopausal Japanese women.
Methods:   The question of whether a polymorphism of the TNFR1 gene would correlate with osteoporosis in 320 unrelated healthy postmenopausal women in Japan, was investigated. A single nucleotide polymorphism (SNP) located at Pro12 (CCA to CCG) in exon 1 of TNFR1 was utilized.
Results:   The subjects were categorized into three genotypes: AA, AG, and GG. The frequency of each genotype was 72.2%, 23.8%, and 4.0%, respectively. The association of this polymorphism with BMD of the lumbar spine and total body, and several bone metabolic markers was then examined. Concerning the TNFR1 gene, the AA group had significantly low total body BMD, compared with the AG + GG group (Z score; 0.285 vs 0.568; P  = 0.03), although BMD of the lumbar spine was not statistically different.
Conclusion:   These results suggest an association between this SNP of the TNFR1 gene and BMD, and an involvement of TNFR1 in postmenopausal osteoporosis among Japanese.     

Association between a promoter polymorphism of the paraoxonase PON1 gene and pathologically verified idiopathic Parkinson's disease

Background:  Exposure to pesticide is associated with an elevated risk of Parkinson's disease (PD). Oxidative stress is also implicated in the etiology of PD. Paraoxonase (PON1) detoxifies organophosphates and exhibits antioxidant properties. It was postulated that polymorphisms of the PON1 gene lead to increased risk of PD.
Methods:  The seven polymorphisms of the PON1 gene were typed and neuropathologic examination performed in 360 Japanese people (191 men and 169 women) consecutively autopsied at a general hospital.
Results:  Thirty-three patients (18 men and 15 women) were diagnosed with pathologically verified idiopathic PD (pviPD). The proportion of male patients with pviPD was highest in the AA genotype (29.4%) of the G(−824)A polymorphism, followed by the GA genotype (9.3%), and least in the GG genotype (6.0%). These genotypic distributions and allele frequency were significantly different between male patients with and without pviPD ( P  = 0.021 and P  = 0.012, respectively). The odds ratio for the −824 A allele versus the −824G allele was 2.47 (95% CI 1.23–4.96). No association between pviPD and the PON1 polymorphisms was found in the female patients.
Conclusion:  Possession of the −824A allele may increase the risk of PD in Japanese men.     

Association between insulin resistance and cognitive function in elderly diabetic patients

Background:   Recently, cognitive impairment in elder diabetic subjects has sparked considerable interest. Insulin resistance (IR) is one of the central pathologies in diabetes mellitus, and several studies have shown that IR is associated with cognitive impairment in non-diabetic elderly subjects. However, the involvement of IR in cognitive dysfunction in the diabetic elderly has remained to be elucidated.
Methods:   In the current study we measured IR with the euglycemic insulin clamp technique, and assessed cognitive function in 13 elderly diabetic patients (mean age, 69.1 ± 4.4). Several tests to assess cognitive function including Mini-Mental State Examination (MMSE) were performed, and clinical indices were evaluated. IR was evaluated by metabolic clearance rates (MCR).
Results:   The Spearman's rank correlation coefficient between MCR and MMSE scores was 0.587 ( P  = 0.035). When subjects were divided into two groups at the median MCR (5.0 mL/kg/min), the lower MCR (high IR) group ( n  = 5) had significantly lower MMSE scores than the higher group ( n  = 8). The Spearman's rank correlation coefficient was –0.641 ( P  = 0.018) between hs-CRP and MMSE scores. When subjects were divided into two groups at the median of high-sensitivity C-reactive protein (hs-CRP) (594.0 µg/dL), the higher hs-CRP group ( n  = 6) had significantly lower MMSE scores than the lower group ( n  = 7).
Conclusion:   The current study shows that higher IR measured with the euglycemic insulin clamp technique and higher hs-CRP is associated with lower MMSE scores in non-demented diabetic elderly patients.     

Albumin, Apolipoprotein E-ɛ4 and Cognitive Decline in Community-Dwelling Chinese Older Adults

OBJECTIVES: To examine the association between serum albumin and cognitive impairment and decline in community-living older adults.
DESIGNS: Population-based cohort study, followed up to 2 years; serum albumin, apolipoprotein E (APOE)-ɛ4, and cognitive impairment measured at baseline and cognitive decline (≥2-point drop in Mini-Mental State Examination (MMSE) score). Odds ratios were controlled for age, sex, education, medical comorbidity, hypertension, diabetes mellitus, cardiac disease, stroke, smoking, alcohol drinking, depression, APOE-ɛ4, nutritional status, body mass index, anemia, glomerular filtration rate, and baseline MMSE.
SETTINGS: Local area whole population.
PARTICIPANTS: One thousand six hundred sixty-four Chinese older adults aged 55 and older.
RESULTS: The mean age of the cohort was 66.0±7.3, 65% were women, mean serum albumin was 42.3±3.1 g/L, and mean MMSE score was 27.2±3.2. Lower albumin tertile was associated with greater risk of cognitive impairment in cross-sectional analysis (low, odds ratio (OR)=2.30, 95% confidence interval (CI)=1.31–4.03); medium, OR=1.59, 95% CI=0.88–2.88) versus high ( P for trend=.002); and with cognitive decline in longitudinal analyses: low, OR=1.73, 95% CI=1.18–2.55; medium, OR=1.32, 95% CI=0.89–1.95, vs high ( P for trend=.004). In cognitively unimpaired respondents at baseline (MMSE≥24), similar associations with cognitive decline were observed ( P for trends <.002). APOE-ɛ4 appeared to modify the association, due mainly to low rates of cognitive decline in subjects with the APOE-ɛ4 allele and high albumin.
CONCLUSION: Low albumin was an independent risk marker for cognitive decline in community-living older adults.     

The differential effects of age on the association of KLOTHO gene polymorphisms with coronary artery disease

The Klotho knockout mouse is thought to be a good animal model for human aging. Recent studies have reported on the association of KLOTHO gene mutation with cardiovascular disease in humans. We observed the frequencies of single nucleotide polymorphisms, that is, G-395A in the promoter region, C1818T in exon 4, and a functional variant, KL-VS, of KLOTHO gene in Koreans, and we investigated their relationships with the presence of coronary artery disease (CAD) in patients who had undergone coronary angiograms. A total of 274 subjects who underwent coronary angiograms because of chest pain were enrolled, and their blood pressure, body mass index, fasting blood glucose level, and lipid profiles were measured. Genotypings were performed on samples of their blood with real-time polymerase chain reaction. Two single nucleotide polymorphisms, G-395A and C1818T, complied with Hardy-Weinberg equilibrium. For the KL-VS genotype, 1 homozygote subject for the adverse allele was detected among the entire population (GG for F352V and CC for C370S). When the subjects were classified into 4 groups according to the number of stenotic vessels, there were no differences among the mean values of the cardiovascular risk factors, except for age and the fasting blood glucose levels, which showed a significant difference between that of the normal and the diseased vessel groups. There were no differences in the prevalence of CAD according to the genotypes of the G-395A polymorphism; however, for the C1818T polymorphism, those subjects with the T allele showed a lower prevalence of CAD than those with the CC genotype. When the subjects were divided into 2 groups according to age, in the group younger than 60 years, T allele carriers of the C1818T polymorphism showed a lower prevalence of CAD than did the noncarriers. In the group older than 60 years, A allele carriers of the G-395A polymorphism showed a lower prevalence of CAD than did the noncarriers. On the haplotype analysis, the GG-CC haplotype showed an increased risk for CAD with an odds ratio of 2.594 (95% confidence interval, 1.385-4.858; P = 0.003). Differential effects of age were observed in the association of KLOTHO G-395A and C1818T polymorphisms with CAD in Koreans. The KL-VS variant seems to be rarely found in the Korean population. These results infer the possibility of the KLOTHO gene being a candidate gene of atherosclerosis in humans, and further research on this topic needs to be done.     

Mannose-binding lectin 2 rs11003123 polymor-phism is associated with the development of hepatocellular carcinoma in patients with hepa-titis B-related cirrhosis in the Chinese population

BACKGROUND: Mannose-binding lectin 2 (MBL2) plays a key role in the host immune response, but whether it is associ-ated with hepatocellular carcinoma (HCC) is not clear. The present study aimed to identify the association between MBL2 gene polymorphisms and HCC in patients with hepatitis B virus (HBV)-related cirrhosis in the Chinese population.
METHODS: A single-nucleotide polymorphism of MBL2, rs11003123, was genotyped and analyzed in a case-control study of HBV-related cirrhotic patients with HCC (n=77) and without HCC (n=40).
RESULTS: We found that Child-Pugh proifles, model for end-stage liver disease score, and the incidence of encephalopathy were all higher in the non-HCC group (P<0.05). A signiifcant association between allele mutants and HCC occurrence was demonstrated by allele comparison (A vs G) (OR=0.34; 95%CI: 0.15-0.76;P=0.006). Heterozygous comparison (GA vs GG) revealed that the individuals with GA mutants had a reduced risk of HCC occurrence compared with those with GG wild type (adjusted OR=0.28; 95% CI: 0.10-0.80;P=0.004). In a dominant model (GA+AA vs GG), a decreased risk of HCC occurrence was observed in individuals with variant geno-types (GA and AA) compared with those with the wild type (adjusted OR=0.30; 95% CI: 0.11-0.85;P=0.004). However, no statistically signiifcant associations were observed between rs11003123 and prognosis of patients with HCC after liver transplantation in both recurrence-free survival and overall survival (P=0.449 andP=0.384, respectively).
CONCLUSION: MBL2 rs11003123 polymorphism may be a marker for the risk of HCC occurrence in patients with HBV-related cirrhosis in the Chinese population.     

Association between COX-2-1195G>A polymorphism and gastrointestinal cancer risk: A meta-analysis

AIM To perform a meta-analysis to investigate the association between cyclooxygenase-2(COX-2)-1195GA gene polymorphism and gastrointestinal cancers. METHODS Publications related to the COX-2-1195GA gene polymorphism and gastrointestinal cancers published before July 2016 were retrieved from Pub Med, EMBASE, Web of Science, China Biological Medicine Database, China National Knowledge Infrastructure, and CQVIP Database. Meta-analysis was performed using Stata11.0 software. The strength of the association was evaluated by calculating the combined odds ratios(ORs) and the corresponding 95%CIs. The retrieved publications were excluded or included one by one for sensitivity analysis. In addition, the funnel plot, Begg's rank correlation test, and Egger's linear regression method were applied to analyse whether the included publications had publication bias. RESULTS A total of 24 publications related to the COX-2-1195GA gene polymorphism were included, including 28 studies involving 11043 cases and 18008 controls. The meta-analysis results showed that the COX-2-1195GA gene polymorphism significantly correlated with an increased risk of gastrointestinal cancers, particularly gastric cancer(A vs G: OR = 1.35; AA/AG vs GG: OR = 1.54; AA vs GG/AG: OR = 1.43; AA vs GG: OR = 1.80; AG vs GG: OR = 1.35). Compared to the Caucasian population in America and Europe, the COX-2-1195GA gene polymorphism in the Asian population(A vs G: OR = 1.30; AA/AG vs GG: OR= 1.50; AA vs GG/AG: OR = 1.35; AA vs GG: OR = 1.71; AG vs GG: OR = 1.37) significantly increased gastrointestinal cancer risk. The sensitivity analysis(P 0.05) and the false positive report probability(P 0.2) confirmed the reliability of the results. CONCLUSION The results showed that the COX-2-1195GA gene polymorphism might be a potential risk factor for gastrointestinal cancers. Further validation by a large homogeneous study is warranted.     

瘦素受体基因Lys109Arg多态性与非酒精性脂肪性肝病的关系

目的探讨瘦素受体基因Lys109Arg多态性与非酒精性脂肪性肝病(NAFLD)的关系。方法收集180 例接受体检的成年人,分成2组:(1)NAFLD组117例,男77例,女40例,平均年龄(50．4±13．1)岁;(2)对照组63例,男32例,女31例,平均年龄(49．1±14．5)岁。同时测定身高、体重、臀围、腰围、腹壁脂肪厚度、体脂含量、血压。入选对象均签署知情同意书。试验对象进行空腹采血,血标本用于检测丙氨酸氨基转移酶、甘油三酯、高密度脂蛋白和血糖水平。结果NAFLD患者和正常对照组LEPR基因Lys109Lys、Lys109Arg和Arg109Arg多态性分布差异无统计学意义(x2=1．409,P=0．494)。腹壁脂肪厚度LEPR基因Lys109Lys携带者平均为(4．1± 0．4)cm,Lys109Arg平均为(2．8±0．6)cm,Arg109Arg平均为(2．7±0．7)cm,LEPR基因Lys109Lys携带者明显高于Lys109Arg和Arg109Arg携带者,差异有统计学意义(F 5．197,P=0．006)。血清胆固醇水平LEPR 基因Lys109Lys携带者平均为(5．1±0．4)mmol／L,Lys109Arg平均为(25．5±6．9)mmol／L,Arg109Arg平均为(27．2±8．4)mmol／L,LEPR基因Lys109Lys携带者明显降低,差异有统计学意义(F=8．164,P=0．005)。结论瘦素受体基因Lys109Arg多态性可能参与腹壁脂肪的分布和胆固醇代谢的调节,至于是否参与NAFLD的发病机制尚待进一步研究。     

北京地区汉族妇女瘦素受体基因Gln223Arg多态性和骨密度的关系

目的　探讨瘦素受体基因Gln2 2 3Arg多态性与青年妇女骨峰值和绝经后骨质疏松妇女骨密度的关系。方法　筛选 2 19例健康青年妇女和 10 2例绝经后骨质疏松妇女 ,用双能X线吸收测定法检测研究对象腰椎和髋部的骨密度 ,用PCR 限制性片段长度多态性分析方法检测研究对象的瘦素受体基因Gln2 2 3Arg的基因型。 结果　本研究人群中瘦素受体基因Gln2 2 3Arg基因型及基因频率的分布符合Hardy Weinberg定律 ,提示本研究人群是一个平衡群体。青年妇女组瘦素受体基因Gln2 2 3Arg的GG基因型组腰椎 2～ 4的骨密度高于GA和AA基因型组 [(1.2 13± 0 .12 7) g/cm2 比(1.15 4± 0 .12 4 ) g/cm2 ,P <0 .0 5 ],在股骨颈、Ward三角区、大转子部位各基因型组间骨密度值无统计学差异 ;10 2例绝经后骨质疏松妇女中LEPR基因Gln2 2 3Arg各基因型组间在腰椎 2～ 4、股骨颈、Ward三角区、大转子部位的骨密度值均无统计学差异。偏相关分析进一步表明青年妇女组的瘦素受体基因多态性与腰椎 2～ 4的骨密度相关 (r =- 0 .15 1,P <0 .0 5 )。结论　瘦素受体基因Gln2 2 3Arg的多态性与青年妇女腰椎 2～ 4骨峰值的获得和维持有关 ,可能是骨峰值独立的影响因素 ,等位基因G可能是骨量的保护因子 ,可作为预测汉族妇女骨质疏松发生危险性的遗传     

A single-nucleotide polymorphism in C-type natriuretic peptide gene may be associated with hypertension.

We conducted an association study between genetic variants of C-type natriuretic peptide gene (CNP) and hypertension in a Japanese population. We found four genetic variants, two in the promoter region, one missense mutation, and one in the 3'-untranslated region (3'-UTR), and genotyped all four variants in 2,006 subjects recruited from the Suita study. One of the variants, G2628A in 3'-UTR, was found to be associated with blood pressure. Multiple logistic analyses indicated that the genotype of the G2628A polymorphism (GG=1, GA+AA=2) (p=0.0034), sex (p=0.0288), alcohol consumption (p=0.0002), age (p<0.0001), and body mass index (p<0.0001) were predictors of hypertension. The odds ratio of the GA+AA genotype over the GG genotype for hypertension was 1.40 (p=0.0034, 95% confidence interval (CI) 1.12-1.75). Multiple logistic analyses in a younger subpopulation aged below 65 years indicated that the odds ratio of the GA+AA genotype over the GG genotype for hypertension was 1.58 (p=0.0024, 95%CI 1.18-2.12). Thus, the CNP G2628A polymorphism made an even greater contribution to hypertension in the younger subpopulation.     

高血压患者血小板聚集功能与纤维蛋白原基因多态性的相关性研究

目的观察高血压患者血小板聚集功能变化是否与Bβ纤维蛋白原(Fib)基因启动子区-455G/A多态性有关。方法选取108例未经治疗的高血压患者,采用全血电阻抗法测定二磷酸腺苷(ADP)及花生四烯酸(AA)诱导的血小板聚集功能,并用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法测定BβFib基因启动子区-455G/A多态性,将其分为GG组和GA+AA组,比较两组血小板聚集功能变化。结果GA+AA组Fib浓度高于GG组(P<0.05),ADP诱导的血小板聚集能力GA+AA组低于GG组(P<0.05);而AA诱导的血小板聚集能力呈现GA+AA组高于GG组的趋势(P>0.05)。结论ADP诱导的血小板聚集功能与BβFib基因启动子区-455G/A多态性有关,GG基因型患者血小板聚集功能强于AA及GA基因型患者。但AA诱导的血小板聚集功能与其的关系呈现相反的趋势。     

Cognitive profiles and response to donepezil treatment in Alzheimer's disease patients

Background:   The aim of this study was to determine whether there are certain characteristic neuropsychological profiles, assessed by the Mini-Mental State Examination (MMSE) at baseline, which predict donepezil treatment response.
Methods:   A total of 112 consecutive outpatients with Alzheimer's disease (AD) were treated with donepezil for 3–4 months. Multiple regression analysis was performed to estimate the relative contributions of individual subscales at baseline to the MMSE change (study point – baseline). To identify the characteristic patterns in cognitive deficits of patients with AD who responded to donepezil therapy, the subscales of the MMSE at baseline of responders and non-responders were compared.
Results:   Multiple regression analysis revealed that lower scores on attention and calculation, and language function, and a higher scale on orientation (date) are related to an improvement of the MMSE. When an improvement of 4 or more points on the MMSE score was defined as a significant response, responders scored significantly lower than non-responders on attention and calculation, whereas non-responders scored significantly lower than responders on memory.
Conclusion:   Our results suggest that individual differences in patterns of neuropsychological impairments may partly contribute to the diversity of the response to donepezil treatment. Although further studies with more detailed neuropsychological tests are needed to confirm our results, the MMSE may add to the prediction of response to donepezil treatment in patients with AD.     

Interleukin-10–592C/A, –819C/T and –1082A/G promoter variants affect the susceptibility to nephropathy in Tunisian type 2 diabetes (T2DM) patients

Background  The Interleukin (IL)-10 polymorphic variants –1082G/A, –819C/T and –592C/A were linked with obesity, metabolic syndrome, and type 2 diabetes (T2DM). We investigated the hypothesis that IL-10 promoter polymorphisms may be associated with the progression of diabetic nephropathy (DN).
Design  Case-controlled study.
Patients  Study subjects comprised of 515 DN patients, and 402 normoalbuminuric (DWN) T2DM patients.
Measurements  IL-10 genotyping was done by PCR-based assays, and the contributions of the IL-10 polymorphic variants to DN were analysed by haplotype analysis and multivariate regression analysis.
Results  Decreased prevalence of (mutant) –819T allele and –819C/T genotype was seen in DN patients; neither the –1082G/A nor the –592C/A polymorphism was associated with DN. Three-loci haplotype (–1082GA/–819CT/–592CA) analysis identified GTC as DN-protective haplotype. Multivariate regression analysis confirmed the association of GTC haplotype ( P =  0·045; O R  = 0·56, 95% CI: 0·31–0·99), and in addition identified GTA haplotype ( P =  0·044; O R  = 0·54, 95% CI: 0·30–0·98) as independent predictors of DN after controlling for a number of covariates (age, sex, BMI; hypertension, glucose, HbA1c, DN duration, total cholesterol, medications).
Conclusion  This study suggests that IL-10 promoter polymorphism influence the risk of nephropathy in Tunisian T2DM patients.     

Association between senescence-related uncoupling protein 2 gene polymorphisms and abdominal obesity in Japanese subjects: The Tanno and Sobetsu study

Background:   Uncoupling protein 2 ( UCP2 ) plays an important role in regulating body weight, energy expenditure and insulin secretion. UCP2 is upregulated in white fat in response to fat feeding, and negatively controls insulin secretion. UCP2 also has a function that protects cells from apoptosis and oxidative stress, which shows UCP2 might be a senescence-related gene. Previously, UCP2 -866G/A polymorphism in the promoter region has been reported to alter adipose tissue mRNA expression and is associated with obesity in Caucasians.
Methods:   In this study, we investigated the association between this polymorphism and obesity, insulin secretion and hypertension in the general Japanese population.
Results:   The allele frequency of UCP2 -866G/A polymorphism was significantly higher in Japanese subjects compared to Caucasians. It revealed that subjects only in the obese group with the AA type of UCP2 -866G/A polymorphism had significantly higher levels of body mass index (BMI) and waist circumference. Multiple logistic regression analysis showed that this polymorphism was independently associated with waist circumference. This positive association remained in the analysis of the subgroup younger than 65 years, but not in the older group. This polymorphism did not affect levels of insulin and homeostasis model assessment ratio (HOMA-R).
Conclusions:   These results suggest that the AA type of UCP2 -866G/A polymorphism is related to abdominal obesity, which indicates the possible role of this polymorphism in causing metabolic syndromes.