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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.

SUBMITTER: Gharooi Ahangar O

PROVIDER: S-EPMC7423921 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Gharooi Ahangar Omid O Javanrouh Niloufar N Daneshpour Maryam S MS Barzin Maryam M Valizadeh Majid M Azizi Fereidoun F Hosseinpanah Farhad F

Scientific reports 20200812 1

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 statu ...[more]

PMID: 32788640

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Project description:BackgroundNon-participation in cohort studies, if associated with both the exposure and occurrence of the event, can introduce bias in the estimates of interest. This study aims to identify factors associated with follow-up participation in Tehran Lipid and Glucose Study, a large-scale community-based prospective study in West Asia.MethodsA sample of 10,368 adults from TLGS was included in the analysis. All analyses were split according to sex and age groups (20-39, 40-59, and 60 years). The associations between socio-demographic, health, and lifestyle factors with response rate were identified using the Generalized Estimating Equations model.ResultsOver the median of 15.7 years of follow up the response rate was 64.5%. The highest response rate was observed in those aged 40-59 years for both sexes. Current smokers had lower odds of response in both sexes for all age groups, ranging from 0.51 to 0.74, p < 0.01. In young adults, being single (OR = 0.79, OR = 0.57, p ≤ 0.01, respectively for men and women) and unemployed (OR = 0.73, OR = 0.76, p ≤ 0.01, respectively for men and women) in both sexes, high physical activity in men (OR = 0.77, p < 0.01), high education (OR = 0.75, p = 0.02) and obesity (OR = 0.85, p = 0.05) in women were associated with lower response rate. For the middle-aged group, diabetes in men (OR = 0.77, p = 0.05) and hypertension (OR = 0.84, p = 0.05), and having a history of cancer (OR = 0.43, p = 0.03) in women were factors associated with lower response rates. Finally, interventions for both sexes (OR = 0.75, OR = 0.77, p ≤ 0.05, respectively for men and women) and being divorced/widow in women (OR = 0.77, p = 0.05) were the factors associated with the lower response rate in the elderly.ConclusionsLong-term participation was influenced by socio-demographic, health, and lifestyle factors in different sex- and age-specific patterns in TLGS. Recruitment strategies targeting these factors may improve participant follow-up in longitudinal studies.

Project description:The complexity of obesity and onset and susceptibility of cardio-metabolic disorders are still poorly understood and is addressed here through studies of genetic influence on weight gain and increased metabolic risk longitudinally.Twenty seven previously identified obesity, eating disorder or metabolic risk susceptibility SNPs were tested for association with weight or metabolically related traits longitudinally in 3999 adults participating both in the HUNT2 (1995-97) and HUNT3 (2006-08) surveys. Regression analyses were performed with changes from normal weight to overweight/obesity or from metabolically healthy to adverse developments with regards to blood pressure, glucose, HDL cholesterol, triglycerides or metabolic syndrome as outcomes. Additionally, a sub-sample of 1380 adolescents was included for testing association of nine SNPs with longitudinal weight gain into young adulthood.The most substantial effect on BMI-based weight gain from normal to overweight/obesity in adults was observed for the DRD2 variant (rs6277)(OR: 0.79, 95% CI: 0.69-0.90, P = 3.9x10(-4), adj. P = 0.015). DRD2 was not associated with BMI on a cross-sectional level. In the adolescent sample, FTO (rs1121980) was associated with change to overweight at adulthood in the combined male-female sample (OR: 1.27, 95% CI: 1.09-1.49, P = 3.0x10(-3), adj. P = 0.019) and in females (OR: 1.53, 95% CI: 1.23-1.91, P = 1.8x10(-4), adj. P = 0.003). When testing for association to longitudinal adverse developments with regard to blood pressure, blood lipids and glucose, only rs964184 (ZNF259/APOA5) was significantly associated to unfavourable triglyceride changes (OR: 1.66, 95% CI: 1.36-2.03, P = 5.7x10(-7), adj. P = 0.001). Pleiotropic effects on metabolic traits, however, were observed for several genetic loci cross-sectionally, ZNF259/APOA5, LPL and GRB14 being the most important.DRD2 exhibits effects on weight gain from normal weight to overweight/obesity in adults, while, FTO is associated to weight gain from adolescence to young adulthood. Unhealthy longitudinal triglyceride development is strongly affected by ZNF259/APOA. Our main finding, linking the DRD2 variant directly to the longitudinal weight gain observed, has not previously been identified. It suggests a genetic pre-disposition involving the dopaminergic signalling pathways known to play a role in food reward and satiety linked mechanisms.

Project description:ObjectivesThe aim of the present study was to evaluate the prevalence of polycystic ovary syndrome (PCOS), its phenotypical and cardio-metabolic features in a community sample of the Iranian population in comparison to healthy eumenorrheic, non-hirsute women without polycystic ovaries. The second aim was to assess the cardio-metabolic characteristics of women who suffered from one criteria of PCOS compared to those healthy eumenorrheic, non-hirsute women.MethodsIn this cross-sectional population-based study, a total of 1,960 eligible women, aged (18-45 years) were recruited from the Tehran-Lipid and Glucose-Study participants and were classified as the three groups of (i) women with PCOS by the Rotterdam criteria, (ii) non-PCOS women with one criteria of PCOS and (iii) healthy eumenorrheic, non-hirsute women without polycystic ovaries morphology (PCOM) as the control group. Further PCOS women were extended to four phenotypes of hyperandrogenism, oligo-anovulation, polycystic ovaries (phenotype A), hyperandrogenism, oligo/anovulation (phenotype B), hyperandrogenism, polycystic ovaries (phenotype C) and oligo-anovulation, polycystic ovaries (phenotype D). Cardio-metabolic profiles and the prevalence of comorbidities of metabolic syndrome (MetS) and lipid abnormalities were compared among these groups linear, and the median regression models adjusted for age and body mass index.ResultsThe prevalence of PCOS according to the diagnostic criteria of the NIH, Rotterdam and AE-PCOS Society were 13.6, 19.4, and 17.8, respectively. Among those who met the Rotterdam criteria, 23.9, 46.3, 21.6, and 8.2% had phenotypes A, B, C, and D, respectively. Among the remaining 1,580 women who did not fulfil the PCOS criteria, 108 (6.8%) suffered from only oligo/anovulation, 332 (21%) only hyperandrogenism/hyperandrogenemia, 159 (16.2%) only PCOM in ultrasound and 981 (62%) were healthy eumenorrheic, non-hirsute women without PCOM. The study revealed that some adiposity indices and lipid abnormalities in PCOS phenotypes with hyperandrogenism (A, B, and C) were worse than in healthy women. By contrast, women with phenotype D did not differ from the healthy ones in terms of adiposity and lipid abnormalities. However, the respective values for other cardio-metabolic profiles and MetS rates in different phenotypes of PCOS were similar to the healthy women. Only the prevalence of MetS in phenotype A was significantly higher than in the healthy women. There were no statistically significant differences between participants with one criteria of PCOS and healthy counterparts in terms of most adiposity indexes, cardio-metabolic factors, and comorbidity of MetS and its components. However, women with hyperandrogenism had a significantly higher level of the waist to height ratio (WHtR) and hypertriglyceridemia than their healthy counterparts.ConclusionPCOS, mainly classical phenotypes A and B, are common among Iranian women of reproductive age. Women with PCOS who had androgen excess exhibited the worst lipid profile, and those who had full three criteria of the syndrome exhibited the higher rate of MetS. However, women with only ovulatory dysfunction and only PCOM had similar cardio-metabolic characteristics, compared to healthy subjects. These data suggest that routine screening for metabolic disturbances may be needed in the prevention of cardio-metabolic disorders in patients with more serious phenotypes of PCOS.

Project description:Rodent and nonhuman primate studies indicate that developmental programming by reduced perinatal nutrition negatively impacts life course cardio-metabolic health. We have developed a baboon model in which we feed control mothers (CON) ad libitum while nutrient restricted mothers are fed 70% of ad libitum global feed in pregnancy and lactation. Offspring of nutrient restricted mothers are intrauterine growth restricted (IUGR) at term. By 3.5 years IUGR baboons showed signs of insulin resistance, indicating a pre-diabetic phenotype, in contrast to healthy CON offspring. We hypothesized that a novel breath analysis approach would provide markers of the altered cardio-metabolic state in a non-invasive manner. Here we assess whether exhaled breath volatile organic compounds (VOCs) collected from this unique cohort of juvenile baboons with documented cardio-metabolic dysfunction resulting from in utero programming can be detected from their breath signatures. Breath was collected from male and female CON and IUGR baboons at 4.8 ± 0.2 years (human equivalent ?13 years). Breath VOCs were quantified using a two-dimensional gas chromatography mass spectrometer. Two-way ANOVA, on 76 biologically relevant VOCs identified 27 VOCs (p < 0.05) with altered abundances between groups (sex, birthweight, and sex x birthweight). The 27 VOCs included 2-pentanone, 2-octanone, 2,2,7,7-tetramethyloctane and 3-methyl-1-heptene, which have not previously been associated with cardio-metabolic disease. Unsupervised principal component analysis of these VOCs could discriminate the four clusters defining males, females, CON and IUGR. This study, which is the first to assess quantifiable breath signatures associated with cardio-metabolic programing for any model of IUGR, demonstrates the translational value of this unique model to identify metabolites of programmed cardio-metabolic dysfunction in breath signatures. Future studies are required to validate the translatability of these findings to humans.

Dataset Information

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

Publications

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

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