Evaluation of the safety and efficacy of amrinone in chronic obstructive lung disease with cor pulmonale

In a pilot study the effect of a bolus dose of amrinone intravenously (IV), 0.5 or 1 mg/kg body weight, in 10 patients with chronic obstructive lung disease and cor pulmonale was evaluated. We found that the higher dose of 1.0 mg/kg IV significantly (P less than 0.05) decreased the mean pulmonary artery pressure and pulmonary wedge pressure without significant changes in cardiac output, in systemic blood pressure or in arterial blood gas values. No adverse effects were recorded in any of the patients.     

Association between the T-381C polymorphism of the brain natriuretic peptide gene and risk of type 2 diabetes in human populations

Brain natriuretic peptide (BNP/NPPB) is a member of the natriureticfamily involved in the regulation of blood pressure and bloodvolume as well as lipolysis control in human fat cells. ThusBNP may play a role in energy metabolism and metabolic diseases.We therefore assessed the association between the BNP promoterT-381C polymorphism and risk of type 2 diabetes and metabolicand BNP expression traits in several population samples. InFrench population-based samples (n = 3216), we found that individualsbearing the -381CC genotype had lower (P = 0.005) fasting glucoselevels than -381TC or -381TT individuals. Moreover, the -381CCgenotype was less frequent in individuals with type 2 diabetes(n = 280, 13.6%) or with impaired fasting glucose (n = 248,12.9%) compared with normoglycaemic individuals (n = 2485, 17.8%).The adjusted odds ratio (OR) (95% CI) of type 2 diabetes for-381CC individuals was 0.69 (0.47–1.00), P = 0.05, whencompared with -381T allele bearers. We replicated this associationin four additional case–control studies for type 2 diabetes.The overall OR (95% CI) of type 2 diabetes was 0.85 (0.76–0.96),P = 0.008, (under a recessive model) (3593 cases and 6646 controlsin total). We also found that the -381C allele was associatedwith higher plasma BNP concentrations (P = 0.015, n = 634) andhigher BNP promoter activity in reporter gene assays. Collectively,these data suggest that relatively high BNP expression may protectagainst type 2 diabetes in humans.     

Impact of polymorphisms of the human beta2-adrenoceptor gene on obesity in a French population

OBJECTIVE: To investigate the impact of two common polymorphisms in the human beta2-adrenoceptor gene (Gly16Arg and Gln27Glu substitutions) on obesity and anthropometric measurements as well as blood variables in a large sample of a French population. DESIGN AND SUBJECTS: Within the framework of the WHO-MONICA project, a population study composed of 1195 subjects aged 35-64 y was randomly sampled from the electoral rolls of the Urban Community of Lille, in northern France. Subjects without any medical treatment (for hypercholesterolaemia, hypertension or diabetes mellitus) susceptible to interfere with body weight and biological variables were selected (n = 836, 419 men/417 women, age = 49.5+/-8.1 y, body mass index (BMI) = 25.7+/-4.4 kg/m2). Subjects with a body mass index > or = 30 kg/m2 were considered as obese (n = 119, age = 49.5+/-8.2 y, BMI = 33.9+/-3.3 kg/m2 range 30-44). MEASUREMENTS: Genotyping was carried out with allele-specific oligonucleotides hybridization. Association between genotypes and various obesity markers (body weight, body mass index, waist and waist-to-hip ratio), lipid, glucose and insulin variables were studied. RESULTS: The Gly16Arg and Gln27Glu polymorphisms were in complete linkage disequilibrium. Gln27Gln subjects had an increased risk of obesity (odds ratio (OR) = 1.77, 95% CI 1.19-2.62, P = 0.005). This effect was mainly detected in men (OR = 2.40, 95% CI 1.34-4.27, P = 0.003). Men bearing the Gln27Gln genotype had higher body weight, BMI, waist and hip circumferences and waist-to-hip ratio than others. Moreover, if Gln27Gln men carried in addition the Arg16 allele, the increase in body weight, BMI and waist-to-hip ratio was more important. CONCLUSION: Our results suggest that genetic variability of the beta2-adrenoceptor gene is implicated in body weight regulation and in the onset of obesity in French men.     

Associations of common SNPs in the SORT1, GCKR,LPL, APOA1, CETP,LDLR, APOE genes with lipid trait levels in an Algerian population sample

Genome-wide association studies have identified many lipid-associated loci primarily in European and Asian populations. In view of the differences between ethnic groups in terms of the frequency and impact of these variants, our objective was to evaluate the relationships between eight lipid-associated variants (considered individually and in combination) and fasting serum triglyceride, total cholesterol, HDL- and LDL-cholesterol levels in an Algerian population sample (ISOR study, n = 751). Three SNPs (in SORT1, CETP and GCKR) were individually associated with lipid level variations. Moreover, the risk allele scores for total cholesterol, triglyceride and LDL-C levels (encompassing between three and six SNPs) were associated with their corresponding lipid traits. Our study is the first to show that some of the lipid-associated loci in European populations are associated with lipid traits in Algerians. Although our results will have to be confirmed in other North African populations, this study contributes to a better understanding of genetic susceptibility to lipid traits in Algeria.     

Study of estrogen receptor-α and receptor-β gene polymorphisms on Alzheimer's disease

Estrogen treatment can modulate the risk for developing dementia in women. Therefore, single nucleotide polymorphisms (SNPs) in the estrogen receptor genes may constitute genetic susceptibility factors to Alzheimer's disease (AD). Thus, we investigated the impact of the genetic variability of the estrogen receptor α 1 (ESR1) and estrogen receptor α 2 (ESR2) genes on late onset AD risk. We analyzed 39 SNPs in ESR1 and 5 SNPs in ESR2 in a French case-control study of sporadic AD (1007 cases/647 controls). Individuals carrying the minor allele of rs7450824 had a lower risk of AD than homozygous subjects for the major allele (age, gender, and APOE ε4 allele adjusted odds ratio = 0.71 [0.57-0.89], p = 0.003). However, this association did not resist Bonferroni correction for multiple testing (p-threshold < 0.001). Consistently, no significant association could be detected when considering age of onset. We also tested for possible interactions between the ESR SNPs and APOE status (ε4 allele) or gender but no significant interaction could be observed. Even after stratifying the sample on APOE status or gender, no significant association with AD risk could be detected. Finally, we searched for potential gene-gene interactions between ESR1 and ESR2 SNPs but no significant interaction could be detected. Our results reinforce the notion that SNPs in the ESR1 or ESR2 genes do not seem to play a major role in the genetic susceptibility of AD.