Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients

BACKGROUND: Reactive oxygen species may contribute to the pathogenesis of asthma. Functional genetic polymorphisms of antioxidant enzymes, superoxide dismutase (SOD) and catalase are good candidates for asthma susceptibility. OBJECTIVE: To investigate the association of the manganese-containing form of SOD (MnSOD) gene at amino acid position 16 (Val16Ala) and catalase gene in the promoter at A-21T and C-262T polymorphisms and asthma in a Hong Kong Chinese population. METHODS: The association study was conducted in a case-control design in asthma patients (n=251) and healthy controls (n=316) by genotyping. The functional significance was assessed by determining erythrocyte SOD and catalase activity. RESULTS: The Val allele of MnSOD at Val16Ala and the A allele of catalase gene at A-21T were not different between patients and controls, while the C allele of catalase gene at C-262T was found to be significantly different between patients and controls (P=0.033). The less frequent variant of catalase gene (-262T) was found to be protective from the development of asthma in a Hong Kong Chinese non-smoking population (adjusted odds ratio=0.35, 0.15-0.85; P=0.017). Asthma patients had elevated erythrocyte SOD and catalase activities in comparison with healthy controls (P<0.01). However, their activities were not associated with different genotypes within healthy controls or asthma patients. CONCLUSION: This is the first report showing that SOD and catalase functional activities are not associated with their respective genetic polymorphisms but related to the presence of asthma in a Hong Kong Chinese population.     

阳城县居民吸烟状况调查分析

对阳城县3646名15岁以上人群吸烟状况分析表明,男性吸烟率63.71％,女性吸烟率0.64％,男女合计吸烟率31.49％,并对不同年龄、职业、文化程度与吸烟率的关系进行了分析。吸烟心理动机:“烟草成瘾”占32.06％,“消遣”占28.48％,“解除疲劳”占16.90％,“交际”占22.56％。吸烟人群的4周患病率和慢性病患病率均高于不吸烟人群,两组差别有显著性(P<0.05,P<0.001)。     

Is there a ‘Basque’ profile regarding autosomal recessive deficiencies of coagulation factors?*

When excluding haemophilia and von Willebrand disease, coagulation factors deficiencies constitute rare autosomal recessive disorders (<1 in 500,000) of less precisely defined epidemiology. We have reported herein the distribution of these entities in the French Basque Country, a genetic isolate of very old individualization with peculiar biological specificities. The prevalence of these disorders was markedly high, especially, as already shown, factor XI deficiency. This unusual profile needs to be discussed in the view of population genetics.     

Evaluation of hypothesis testing for comparing two populations using NONMEM analysis

In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i)the ratio of mean clearance and (ii)the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.Partial support from the Upjohn Company, NIH-BRSG SO RR 07066, and the Burroughs Wellcome Foundation.     

Complex segregation analyses of bone mineral density in Chinese

China has the largest population in the world; approximately 7% of the total population suffers from primary osteoporosis. Osteoporosis is mainly characterized by low bone mineral density (BMD). In the present study, familial correlation and segregation analyses for spine and hip BMDs have been undertaken for the first time in a Chinese sample composed of 401 nuclear families with a total of 1,260 individuals. The results indicate a major gene of additive inheritance for hip BMD, whereas there is no evidence of a major gene influencing spine BMD. Significant familial residual effects are found for both traits, and heritability estimates (±SE) for spine and hip BMDs are 0.807(0.099) and 0.897(0.101), respectively. Sex and age differences in genotype‐specific average BMD are also observed. This study provides the first evidence quantifying the high degree of genetic determination of BMD variation in the Chinese.     

Evolution of accommodative function and development of ocular movements in children

The evolution of the accommodative function and development of ocular movement are evaluated in a non-clinical paediatric population (1056 subjects) aged 6-12 years, providing means for each age in the optometric tests that evaluate the accommodative amplitude, accommodative facility, accommodative response (lag), and saccadic movements. A comparison of these values between ages (anova) established three distinct trends in the behaviour of these parameters. The accommodative amplitude, measured by modified dynamic retinoscopy, and the evaluation of the saccadic movements by the development of ocular movements [developmental eye movement (DEM)] test showed continuous change with age. The values for monocular and binocular accommodative facility, measured by +/-2.00 D flippers, indicated the need to divide the population into two age groups (6-7 and 8-12 years). Finally, the means of accommodative response, measured by monocular estimation model (MEM) retinoscopy, and the direct observation of saccadic movement revealed no significant differences between ages, establishing a single mean reference value for the age group studied.     

中国贫困医疗救助模式的制度缺陷及其改进思路

讨论现行国内医疗救助模式的基本经验与存在的缺陷。现行国内医疗救助模式无论在制度设计还是具体实施中部存在许多缺陷，如在制度设计方面，救助标准与水平总体上都比较低，大病痛种的规定大大限制和缩小了贫困医疗救助的范围，而定点医院限制了救助对象选择的空间等。     

全国部分城乡家鼠鼠情监测三年结果分析——Ⅰ.鼠种组成及地区分布

对全国部分城乡家鼠鼠情监测三年结果的分析表明:城乡家鼠组成均以三大家鼠(褐家鼠、小家鼠、黄胸鼠)为主,其次为食虫目臭鼩鼱~#和黑线姬鼠。五种主要鼠种在家鼠组成中的数量比基本稳定,但三年中城乡少数鼠种间的顺位有所变化。监测结果亦表明,五种主要鼠种的地区分布是:褐家鼠、小家鼠遍布所有监测的省、市、区,同以往文献中遍布全国的说法一致;黄胸鼠分布于黄河以南;食虫目中的臭鼩鼱分布于华中区以南的广大地区。这在以往文献中均已有记载,但以往文献有关黄胸鼠和臭鼩鼱分布的其他说法,则被证实为不确切的。黑线姬鼠的分布范围已超过以往文献中关于分布于东北、华北及长江流域的说法,但以往文献中关于该鼠种遍及全国的说法是否正确,则有待进一步证实。     

Simulation for population analysis of Michaelis-Menten elimination kinetics

A simulation study was conducted to compare the cost and performance of various models for population analysis of the steady state pharmacokinetic data arising from a one-compartment model with Michaelis-Menten elimination. The usual Michaelis-Menten model (MM) and its variants provide no estimate of the volume of distribution, and generally give poor estimates of the maximal elimination rate and the Michaelis-Menten constant. The exact solution to the Michaelis-Menten differential equation (TRUE) requires a precise analysis method designed for estimation of population pharmacokinetic parameters (the first-order conditional estimation method) and also considerable computational time to estimate population mean parameters accurately. The one-compartment model with dose-dependent clearance (DDCL), in conjunction with the first-order conditional estimation or Laplacian method, ran approximately 20-fold faster than TRUE and gave accurate population mean parameters for a drug having a long biological half-life relative to the dosing interval. These findings suggest that the well-known MM and its variants should be used carefully for the analysis of blood concentrations of a drug with Michaelis-Menten elimination kinetics, and that TRUE, in conjunction with a precise analysis method, should be considered for estimating population pharmacokinetic parameters. In addition, DDCL is a promising alternative to TRUE with respect to computation time, when the dosing interval is short relative to the biological half-life of a drug. This work was supported in part by the Epilepsy Research Foundation, the Nakatomi Foundation, and a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan.