Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians

Copyright: Copyright 2008 Elsevier B.V., All rights reserved.The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.publishersversionPeer reviewe

Association of Adiponectin SNP+45 and SNP+276 with Type 2 Diabetes in Han Chinese Populations: A Meta-Analysis of 26 Case-Control Studies

Recently, many studies have reported that the SNP+45(T>G) and SNP+276(G>T) polymorphisms in the adiponectin gene are associated with type 2 diabetes (T2DM) in the Chinese Han population. However, the previous studies yielded many conflicting results. Thus, a meta-analysis of the association of the adiponectin gene with T2DM in the Chinese Han population is required. In the current study, we first determined the distribution of the adiponectin SNP+276 polymorphism in T2DM and nondiabetes (NDM) control groups. Our results suggested that the genotype and allele frequencies for SNP+276 did not differ significantly between the T2DM and NDM groups. Then, a meta-analysis of 23 case-control studies of SNP+45, with a total of 4161 T2DM patients and 3709 controls, and 11 case-control studies of SNP+276, with 2533 T2DM patients and 2212 controls, was performed. All subjects were Han Chinese. The fixed-effects model and random-effects model were applied for dichotomous outcomes to combine the results of the included studies. The results revealed a trend towards an increased risk of T2DM for the SNP+45G allele as compared with the SNP+45T allele (OR = 1.34; 95% CI, 1.11–1.62; P<0.01) in the Chinese Han population. However, there was no association between SNP+276 and T2DM (OR = 0.90; 95% CI, 0.73–1.10; P = 0.31). The results of our association study showed there was no association between the adiponectin SNP+276 polymorphism and T2DM in the Yunnan Han population. The meta-analysis results suggested that the SNP+45G allele might be a susceptibility allele for T2DM in the Chinese Han population. However, we did not observe an association between SNP+276 and T2DM

The Influence of Personality Traits on the Relationship between Bullying at Work, Health Complaints and Absenteeism

Aim: Bullying and harassment at work is widespread and could have negative effects on both the victims and the organizations in which it occurs. Literature about the influence of the personality of the victims on health outcomes is scarce. Starting from the Michigan Stress Model (Caplan, Cobb, French, Pinneau, &amp; Van Harison, 1975), we investigated the relationships between the Big Five personality traits, being bullied at work, physical health complaints and absenteeism. Bullying is defined in this paper as the repeated, systematic, intentional negative behavior of one or more individuals directed at another individual (Olweus,1993). A distinction was made between person-related bullying, e.g. giving names, insulting and gossiping, and work-related bullying, e.g. giving unreasonable deadlines or too much or too few work. We expected victimization to have a significant positive relationship with health complaints and absenteeism. Personal traits were assumed to moderate both relationships. Method: An online survey with validated self-report questionnaires among 2650 Belgian government employees (age range 18-65, response rate = 41%, 36 % male, 64 % female) was conducted. Bullying was measured with the Negative Acts Questionnaire (NAQ, α= .92), the personality traits with the NEO-Five Factor Inventory (NEO-FFI, α= .88 - .94 ), physical health complaints with the Dutch version (VOEG) of the Questionnaire Research Experienced Health (α= .88) and absenteeism with one item of Questionnaire Organizational Stress-D (VOS-D). Results and conclusions: Hierarchical regression analysis showed that both work-related bullying and person-related bullying influenced reported physical health negatively. Contrary to our hypothesis the personality traits did not moderate this relationships. A correlation was found between person-related (but not work-related) bullying and absenteeism: victimized employees were more absent compared to non-victimized colleagues. The personality trait openness moderated this relationship. Opposite to our expectations the relation between being bullied and absenteeism was stronger for employees who score high on openness. In addition it was found that the personality traits neuroticism and conscientiousness partly mediated the relationship between being bullied (total bullying) and health complaints, but not that between being bullied and absenteeism. Those correlations are positive: being bullied is related with higher scores on neuroticism and conscientiousness and with more health complaints. These results illustrate the need for future studies into the influence of personality traits on the effects of bullying on victims and show the relevance of the difference between person-related and work-related bullying. Caplan, R.D., Cobb, S., French, J.R.D., Pinneau, Jr, S.R. &amp; Van Harison, R. (1975) Job demands and worker health; main effects and occupational differences. Cincinnati, OH. National Institute of Occupational Safety and Health (publication 75-168). Olweus, D. (1993) Bullying at school: What we know and what we can do. Malden: Blackwell

Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients.

Permanent neonatal diabetes (PND), requiring insulin within the first months of life, is unexplained at the molecular level in most cases. It has very recently been shown that heterozygous activating mutations in the KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive K(+) channel involved in the regulation of insulin secretion, cause PND. In the present study, we screened the KCNJ11 gene for mutations in French patients with PND. Patients were recruited through the French network for the study of neonatal diabetes. Seventeen at-term babies with a median age at diagnosis of diabetes of 64 days (range 1-260) were included. We identified in nine patients seven heterozygous nonsynonymous mutations: three of them (V59M, R201C, and R201H) were already described, and the four novel mutations resulted in an amino acid change of Kir6.2 at positions F35L, G53N, E322K, and Y330C. More patients with a Kir6.2 mutation (six of nine) were reported to have a smaller birth weight than those without mutation (two of eight). Although Kir6.2 mutation carriers do not represent a phenotypically specific form of PND, an impaired function of Kir6.2 is associated with in utero insulin secretory insufficiency and growth retardation. In conclusion, we confirmed that Kir6.2 mutations are a common cause (53%) of PND in Caucasians