Dataset Information

Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults.

ABSTRACT: Recent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index. The aim of the present study was to compare the frequencies of mtDNA haplogroups as well as control region (CR) polymorphisms of obese juveniles (n = 248) and obese adults (n = 1003) versus normal weight controls (njuvenile = 266, nadults = 595) in a well-defined, ethnically homogenous, age-matched comparative cohort of Austrian Caucasians.Using SNP analysis and DNA sequencing, we identified the nine major European mitochondrial haplogroups and CR polymorphisms. Of these, only the T haplogroup frequency was increased in the juvenile obese cohort versus the control subjects [11.7% in obese vs. 6.4% in controls], although statistical significance was lost after adjustment for sex and age. Similar data were observed in a local adult cohort, in which haplogroup T was found at a significantly higher frequency in the overweight and obese subjects than in the normal weight group [9.7% vs. 6.2%, p = 0.012, adjusted for sex and age]. When all obese subjects were considered together, the difference in the frequency of haplogroup T was even more clearly seen [10.1% vs. 6.3%, p = 0.002, OR (95% CI) 1.71 (1.2-2.4), adjusted for sex and age]. The frequencies of the T haplogroup-linked CR polymorphisms C16294T and the C16296T were found to be elevated in both the juvenile and the adult obese cohort compared to the controls. Nevertheless, no mtDNA haplogroup or CR polymorphism was robustly associated with any of several investigated metabolic and cardiovascular parameters (e.g., blood pressure, blood glucose concentration, triglycerides, cholesterol) in all obese subjects.By investigation of this large ethnically and geographically homogenous cohort of Middle European Caucasians, only mtDNA haplogroup T was identified as an obesity risk factor.

SUBMITTER: Ebner S

PROVIDER: S-EPMC4556186 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults.

Ebner Sabine S Mangge Harald H Langhof Helmut H Halle Martin M Siegrist Monika M Aigner Elmar E Paulmichl Katharina K Paulweber Bernhard B Datz Christian C Sperl Wolfgang W Kofler Barbara B Weghuber Daniel D

PloS one 20150831 8

<h4>Background</h4>Recent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index. The aim of the present study was to compare the frequencies of mtDNA haplogroups as well as control region (CR) polymorphisms of obese juveniles (n = 248) and obese adults (n = 1003) versus normal weight controls (njuvenile = 266, nadults = 595) in a well-defined, ethnically homogenous, age-matched comparative cohort of Austrian Caucasian ...[more]

PMID: 26322975

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Project description:ImportanceIt is unknown whether the triglyceride-glucose (TyG) index as a measure of insulin resistance is associated with the risk of developing end-stage kidney disease (ESKD). Because individuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and ESKD risk through the TyG index seems plausible but has not been investigated.ObjectiveTo evaluate whether the TyG index is associated with ESKD risk and, if so, to what extent the TyG index mediates the association between BMI and ESKD.Design, setting, and participantsA total of 176 420 individuals were recruited during routine health examinations to participate in the Austrian Vorarlberg Health Monitoring and Promotion Program (VHM&PP), a prospective, population-based cohort study with participant enrollment between January 1, 1988, and June 30, 2005, and a mean follow-up of 22.7 years. Data analysis was conducted from March 1, 2020, to September 30, 2020.ExposuresBody mass index and the logarithmized product of fasting triglyceride and glucose concentrations (TyG index), as determined during the baseline health examination.Main outcomes and measuresEnd-stage kidney disease, as indicated by initiation of kidney replacement therapy, either dialysis or kidney transplantation.ResultsOf the 176 420 participants, 94 885 were women (53.8%); mean (SD) age was 42.5 (15.4) years. During a mean (SD) follow-up of 22.7 (6.9) years, 454 (0.3%) participants developed ESKD and 35 234 (20.0%) died. In multivariable-adjusted Cox proportional hazards models, the TyG index was significantly associated with the risk of ESKD, both with (hazard ratio [HR] per 1-SD increase, 1.68; 95% CI, 1.56-1.82) and without (HR per 1-SD increase, 1.79; 95% CI, 1.66-1.93) the inclusion of BMI as a covariate. Mediation analysis using a newly proposed 2-stage regression method for survival data showed that a 5-point increase in BMI increased the risk of ESKD by 58% (HR [total association], 1.58; 95% CI, 1.43-1.75), and that 41.7% of the total association (95% CI, 31.6%-51.8%) was mediated through the TyG index (HR [indirect association], 1.21; 95% CI, 1.18-1.25).Conclusions and relevanceThis study found that the TyG index appeared to be associated with ESKD risk and mediates nearly half of the total association between BMI and ESKD in the general population. Public health efforts aiming at the reduction of body weight might decrease the kidney sequelae of insulin resistance and the burden of ESKD.

Dataset Information

Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults.

Publications

Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults.

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