Background The sex-specific aetiology of cardiometabolic risk across the life course is well established but remains poorly understood. Mitochondria are essential for energy conversion in all cells. Mitochondrial DNA haplogroups have been implicated in the aetiology of cardiometabolic risk, though previous studies have not examined whether mitochondrial DNA haplogroups contribute to the sex-specific aetiology of cardiometabolic risk. We examined sex-specific associations between eight common European haplogroups and ten cardiometabolic risk factors in childhood and adolescence.
Methods Longitudinal data from the Avon Longitudinal Parents and Child Study, a prospective birth cohort study, was analysed. Cardiometabolic risk factors included systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, triglycerides, high-density lipoprotein cholesterol (HDL-c), non-HDL-c, insulin, glucose, height-adjusted fat mass and height-adjusted lean mass, measured at research clinics when participants were approximately 7, 9, 10, 11, 13, 15 and 18 years old. Participants were genotyped using the SNP genotyping platform by Sample Logistics and Genotyping Facilities at the Wellcome Trust Sanger Institute and LabCorp (Laboratory Corporation of America). We used linear spline multilevel models to examine the association between mitochondrial DNA haplogroups and cardiometabolic risk factor trajectories across childhood and into adolescence. Analysis was stratified by sex to allow for differential effects between sexes. All trajectories were modelled in MLwiN version 2.36 called from Stata version 15.
Results Sample sizes for different outcomes range from 2,023 females and 1,962 males (6,518 total measures) for insulin up to 3,570 females and 3,689 males (17,039 total measures) for triglycerides. There was no strong evidence that haplogroups H,J,K,U,T and I are associated with cardiometabolic risk factors. In females, haplogroup X was associated with 3.22 mmHg (95% confidence interval (CI):0.4–6.0) lower SBP at age 7 and 1.29 kg (95%CI:0.4–2.2) lower lean mass at age 9 compared with haplogroup H. Similar associations were observed at age 18, albeit with CIs spanning the null. Haplogroup X was also associated with 15.5% (95%CI:2.5–28.5) lower fat mass at age 9 in females, although this association did not persist at age 18. Males with haplogroup W had higher HDL-c and lower non-HDL-c at birth, with decreasing and increasing rates of change, respectively, during the first 9 years of life. The associations did not persist at age 18.
Conclusion Mitochondrial DNA haplogroups X and W may play a role in the sex-specific aetiology of cardiometabolic risk during childhood and adolescence.
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