Genetic markers and continuity of healthy metabolic status: Tehran cardio-metabolic genetic study (TCGS)

Abstract

obese individuals can be categorized as "healthy obese" (MHo) and "unhealthy obese" (MUo) based on the presence or absence of metabolic abnormality. this study sets out to assess potential genetic causes behind persistence of healthy metabolic status in individuals categorized as "healthy obese". This study was conducted in the framework of the Tehran cardio-metabolic genetic study (TCGS). 766 MHO subjects at the start of the study followed up 15 years for occurrence of metabolic unhealthy status. these two groups (persistent MHo, MUo) were compared regarding the presence or absence of 16 single nucleotide polymorphisms (SNPs) identified as being associated with obesity phenotype in previous studies. We used logistic regression model for assessing the association between MHo/ MUO with candidate SNPs. By the end of the follow up, 206 (27%) were categorized as the persistent MHO and 560 (73%) as MUO groups. Considering interaction effect between some SNP and sex, a sex stratification analysis was applied. When the analysis was performed by gender, rs1121980 associated with a decrease, and rs7903146 with an increase in the likelihood of persistent MHO individuals. Another analysis was separately performed on postmenopausal women from both groups; it showed that rs13107325 was associated with an increase in the likelihood of persistent MHO status in this subgroup of woman. In all cases, the markers had dominant inheritance. This findings suggest that the expression of some genetic markers are associated with persistence of healthy metabolic status, in female obese individuals. Obesity and overweight have a clear association with long-term morbidity and mortality 1,2. There is a wide range of heterogeneity among obese individuals with the combination of obesity and metabolic status causing a wide spectrum of obesity phenotypes 3,4. Prevalence of "healthy obese" is reported to be between 9 and 34% in different populations depending on various definitions of metabolic healthy status 5-8. Whether "healthy obese" has a benign course is controversial and different studies have reported varying results 9-12. Some studies have shown that this obesity phenotype is a dynamic entity and in cohort studies up to 50% of individuals who were "healthy obese" turned into "unhealthy obese" at the end of the follow-up period 5-8. Some studies have assessed the predictors of changes in metabolic health in healthy obese individuals. Achilike et al. 13 suggested that lipid profile and insulin resistance predict the metabolic status in obesity. Appleton et al. 6 reported that younger age and lower waist circumference (WC) at baseline of obese individuals were significantly associated with maintaining the metabolic healthy state in a longitudinal follow-up. In addition, a study on Tehranian healthy abdominal obese individuals showed that baseline hypertriglyceridemia, low HDL-C, and HOMA-IR were independent predictors of metabolic changes in this population 5. However, it has been known that obesity and the resulting metabolic abnormality a...

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“…Furthermore, 31 polymorphisms were observed to be located close to at least one other SNP within the same gene or intergenic region, suggesting their special relevance according to the authors. A different study reported a significant association of FTO (rs1121980) and TCF7L2 (rs7903146) genetic variants with maintaining metabolic health in obese women, who did not develop MetS according to joint interim statement criteria[ 27 ]. In addition, a genetic variant of SLC39A8 (rs13107325) was found to have a statistically significant association with metabolic health status in a subgroup of postmenopausal women.…”