Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18–1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7–17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom’s MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P<0.05), and found positive associations between methylation and alanine aminotransferase (ALT) levels adjusted by gender, age and BMI at the position 46801699 (r = 0.226, P = 0.007). These results suggest that HIF3A DNA methylation is associated with childhood obesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD).
BackgroundThe associations of famine exposure with diabetes risk in adulthood are still unclear. This study aimed to explore the association between famine exposure in early life and risk of diabetes in adulthood.MethodsA total of 4138 subjects were selected from the data of the China Health and Retirement Longitudinal Study (CHARLS) 2011–2012. Diabetes was diagnosed as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated haemoglobin (HbA1C) > 6.5%, or self-reported diabetes. Birthdates of subjects were used to categorize famine exposure groups. The association of fetal-stage famine exposure with diabetes risk in adults was assessed using logistics regression model.ResultsThe prevalence of diabetes in the non-exposed, fetal-stage exposed, infant-stage exposed, and preschool-stage exposed groups were 9.0, 13.6, 12.7 and 10.8%, respectively. Compared with the age-balanced control group, the fetal-stage exposed group was associated with the elevated risk of diabetes in later life after adjusting for covariates (OR = 1.37; 95%CI: 1.09–1.72; P = 0.008). Stratified analysis showed that the association between prenatal famine exposure and diabetes risk in adulthood was comparable between severely affected areas and less severely affected areas (P for interaction =0.153).ConclusionsFamine exposure in fetal stages was associated with the elevated diabetes risk in adults, which could be the critical periods for relative intervention.Electronic supplementary materialThe online version of this article (10.1186/s12889-018-6134-x) contains supplementary material, which is available to authorized users.
Carbonic anhydrase (CA) plays a critical role in pH regulation, long-term synaptic transformation, and is associated with mental retardation, Alzheimer's disease (AD), and Down syndrome. There is accumulating evidence that CAII is increased in AD brain. The present study focused on the determination of CAII protein level in blood plasma samples using immunoblot and ELISA methods. We compared plasma from 91 AD patients (average age 74.8 y), 83 persons with amnestic mild cognitive impairment (MCI) (average age 73.7 y), and 113 cognitively normal controls (average age 70.8 y). The plasma level of CAII was significantly increased in AD patients, as compared to control groups. CAII levels were higher in males than females. There was an age-dependent increase of CAII. These results provide further evidence that changes in CAII level may play a role in the pathogenesis of AD.
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