PAI-1 gene 4G/5G polymorphism, cytokine levels and their relations with metabolic parameters in obese children

Kinik, Sibel Tulgar; Özbek, Namık; Yuce, Muammer; Yazıcı, Ayşe Canan; Verdı, Hasıbe; Ataç, Fatma Belgin

doi:10.1160/th07-06-0395

Cited by 19 publications

(6 citation statements)

References 24 publications

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“…While some case-control studies found differences in genotype distribution between obese and non-obese participants [45], [46], others did not [38]. Our data, providing the first population-based evidence, indicated that there were no differences in genotype distribution between individuals of normal weight and those who were overweight/obese.…”

Section: Discussioncontrasting

confidence: 55%

In Black South Africans from Rural and Urban Communities, the 4G/5G PAI-1 Polymorphism Influences PAI-1 Activity, but Not Plasma Clot Lysis Time

Lange

Rijken²,

Hoekstra

et al. 2013

PLoS ONE

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Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

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Section: Discussioncontrasting

confidence: 55%

In Black South Africans from Rural and Urban Communities, the 4G/5G PAI-1 Polymorphism Influences PAI-1 Activity, but Not Plasma Clot Lysis Time

Lange

Rijken²,

Hoekstra

et al. 2013

PLoS ONE

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“…In Children with obesity, Estelles et al [39] observed no influence of the 4 G/5 G polymorphism on PAI-1 levels. Moreover, no influence of the PAI-1 4 G/5 G polymorphism on lipid and glucose metabolism parameters was observed in Turkish obese children [40,41]. …”

Section: Discussionmentioning

confidence: 99%

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

et al. 2012

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BackgroundSeveral association studies have shown that -844 G/A and HindIII C/G PAI-1 polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in PAI-1 gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children.MethodsThis study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95th percentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95th percentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and HindIII C/G PAI-1 polymorphisms were analyzed by PCR-RFLP.ResultsFor the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; p = 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; p = 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; p = 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; p = 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; p = 0.01). The C/G and G/G genotypes of the HindIII C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; p = 0.02) in comparison with C/C genotype.ConclusionsThe -844 G/A PAI-1 polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the HindIII C/G PAI-1 polymorphism was associated with the increase of total cholesterol levels in Mexican children.

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“…[32] On the other hand, Yener et al showed lower levels of TGF-β in obese children without being correlated with lipid or insulin resistance, [33] while another study was also pointing out an indirect proportional relation between serum TGF-β levels, BMI, and waist circumference, respectively. [34] Wong et al [35] proved that the TGF-β1 869T > C (Leu10Pro) gene polymorphism is associated with type 2 diabetes mellitus, pointing out a correlation between the C allele of the TGF-β1 869T > C gene polymorphism and serum TGF-β levels.…”

Section: Introductionmentioning

confidence: 99%

The role of TGF-β1 869 T > C and PPAR γ2 34 C > G polymorphisms, fat mass, and anthropometric characteristics in predicting childhood obesity at birth

Mărginean

Iancu²,

Szabó

et al. 2016

Medicine

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This study proposed to establish a correlation between the risk score for child obesity and anthropometric, genetic, and bioimpedance characteristics in mothers and newborns, and to assess the discriminant ability for anthropometric parameters to classify over-fatness (defined by bioimpedance body fatness %) in pregnant women.We performed a cross-sectional study on 388 couples (mother and father) and their newborns admitted in a Tertiary Hospital from Romania. The measured parameters for mothers and their newborns were risk percentage for child obesity, anthropometric characteristics (mid-upper arm circumference [MUAC], tricipital skinfold thickness [TST] of mother and newborn), genetic polymorphisms (human peroxisome proliferator-activated receptor γ [PPARγ2] 34 C > G and transforming growth factor-beta 1 [TGF-β1] 869 T > C gene polymorphisms in both mothers and newborns), and mother's bioimpedance characteristics (fat mass [FM] %).The obesity risk score according to standard predictable Northern Finland Birth Cohort equation was in our study 4.07%. We found a monotone positive significant correlation between the newborn's risk of childhood obesity and the mother's TST (P = 0.01), as well as a tendency toward statistical significance concerning correlation with mother's MUAC (P = 0.053), without any correlations with the mothers’ bioimpedance parameters and also a positive correlation between the newborn's risk of childhood obesity and the newborn's anthropometrical characteristics like body mass index (BMI), MUAC, and TST (P < 0.001). We observed that the calculated newborn's risk percentage for child obesity was greater for the variant allele of the TGF-β1 869 T > C polymorphism and also for the wild-type C allele of the PPARγ2 34 C > G gene polymorphism. Our study indicated that the best predictors for over-fatness are BMI and MUAC (P = 0.01 < 0.02 and P = 0.019 < 0.02, respectively).

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PAI-1 gene 4G/5G polymorphism, cytokine levels and their relations with metabolic parameters in obese children

Cited by 19 publications

References 24 publications

In Black South Africans from Rural and Urban Communities, the 4G/5G PAI-1 Polymorphism Influences PAI-1 Activity, but Not Plasma Clot Lysis Time

In Black South Africans from Rural and Urban Communities, the 4G/5G PAI-1 Polymorphism Influences PAI-1 Activity, but Not Plasma Clot Lysis Time

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

The role of TGF-β1 869 T > C and PPAR γ2 34 C > G polymorphisms, fat mass, and anthropometric characteristics in predicting childhood obesity at birth

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