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SHBG gene polymorphism (rs1799941) associates with metabolic syndrome in children and adolescents.

White MJ, Eren F, Agirbasli D, Williams SM, Agirbasli M - PLoS ONE (2015)

Bottom Line: In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012), while in cases there was no association between rs1799941 and SHBG levels (p = 0.963).The significant association between rs1799941 and MetS in children is not contingent on any single CM trait.Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children.

View Article: PubMed Central - PubMed

Affiliation: Center for Human Genetic Research, Vanderbilt University, Nashville, Tennessee, United States of America; Department of Genetics, Institute for Quantitative Biomedical Sciences, Dartmouth College, Hanover, New Hampshire, United States of America.

ABSTRACT

Background: Metabolic syndrome (MetS) is a complex disorder characterized by coexistence of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD). The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents.

Methods: Genetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs), previously shown to modulate lipid or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish pediatric cohort (37 cases, 323 controls).

Results: Logistic regression analysis revealed a significant association between rs1799941, located in SHBG, and MetS (OR = 3.09, p-value = 0.006). The association with MetS remained after sequential adjustment for each CM factor included in the syndrome definition, indicating that the identified association is not being driven by any single trait. A relationship between rs1799941 and SHBG levels, was also discovered, but it was dependent on MetS status. In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012), while in cases there was no association between rs1799941 and SHBG levels (p = 0.963).

Conclusions: The significant association between rs1799941 and MetS in children is not contingent on any single CM trait. Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children.

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MetS status and the relationship between rs1799941 and SHBG.Fig. 3 assesses whether MetS status affected the relationship betweenrs1799941 and SHBG. The association with increased circulating SHBGlevels in the full dataset was driven by control subjects only (K-Wp-value = 0.031, NP p-value = 0.012).
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pone.0116915.g003: MetS status and the relationship between rs1799941 and SHBG.Fig. 3 assesses whether MetS status affected the relationship betweenrs1799941 and SHBG. The association with increased circulating SHBGlevels in the full dataset was driven by control subjects only (K-Wp-value = 0.031, NP p-value = 0.012).

Mentions: The minor allele of rs1799941 associated with both increased odds of MetS andincreased circulating SHBG levels. Since previous studies indicated that higherSHBG associated with a decrease in risk of MetS [15], we assessed whether MetS status affected therelationship between rs1799941 and SHBG. Results from our MetS status stratifiedanalyses showed that the association with increased circulating SHBG levels inthe full dataset was driven by control subjects only (K-W p-value = 0.031, NPp-value = 0.012) (Table 7,Figs. 2–3). Because of the significantdifferences in the distributions of age and gender between MetS cases andcontrols (Table 1, S8 Table),we performed explicit tests to evaluate the validity of the observed differencein median/mean SHBG seen between MetS cases and controls when we adjusted forthe effects of age and gender. Median regression analyses revealed that afteraccounting for the effects of age and gender, median SHBG levels were stillsignificantly associated with MetS status (p = 6.48E-09) (S9–10 Tables).


SHBG gene polymorphism (rs1799941) associates with metabolic syndrome in children and adolescents.

White MJ, Eren F, Agirbasli D, Williams SM, Agirbasli M - PLoS ONE (2015)

MetS status and the relationship between rs1799941 and SHBG.Fig. 3 assesses whether MetS status affected the relationship betweenrs1799941 and SHBG. The association with increased circulating SHBGlevels in the full dataset was driven by control subjects only (K-Wp-value = 0.031, NP p-value = 0.012).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380117&req=5

pone.0116915.g003: MetS status and the relationship between rs1799941 and SHBG.Fig. 3 assesses whether MetS status affected the relationship betweenrs1799941 and SHBG. The association with increased circulating SHBGlevels in the full dataset was driven by control subjects only (K-Wp-value = 0.031, NP p-value = 0.012).
Mentions: The minor allele of rs1799941 associated with both increased odds of MetS andincreased circulating SHBG levels. Since previous studies indicated that higherSHBG associated with a decrease in risk of MetS [15], we assessed whether MetS status affected therelationship between rs1799941 and SHBG. Results from our MetS status stratifiedanalyses showed that the association with increased circulating SHBG levels inthe full dataset was driven by control subjects only (K-W p-value = 0.031, NPp-value = 0.012) (Table 7,Figs. 2–3). Because of the significantdifferences in the distributions of age and gender between MetS cases andcontrols (Table 1, S8 Table),we performed explicit tests to evaluate the validity of the observed differencein median/mean SHBG seen between MetS cases and controls when we adjusted forthe effects of age and gender. Median regression analyses revealed that afteraccounting for the effects of age and gender, median SHBG levels were stillsignificantly associated with MetS status (p = 6.48E-09) (S9–10 Tables).

Bottom Line: In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012), while in cases there was no association between rs1799941 and SHBG levels (p = 0.963).The significant association between rs1799941 and MetS in children is not contingent on any single CM trait.Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children.

View Article: PubMed Central - PubMed

Affiliation: Center for Human Genetic Research, Vanderbilt University, Nashville, Tennessee, United States of America; Department of Genetics, Institute for Quantitative Biomedical Sciences, Dartmouth College, Hanover, New Hampshire, United States of America.

ABSTRACT

Background: Metabolic syndrome (MetS) is a complex disorder characterized by coexistence of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD). The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents.

Methods: Genetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs), previously shown to modulate lipid or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish pediatric cohort (37 cases, 323 controls).

Results: Logistic regression analysis revealed a significant association between rs1799941, located in SHBG, and MetS (OR = 3.09, p-value = 0.006). The association with MetS remained after sequential adjustment for each CM factor included in the syndrome definition, indicating that the identified association is not being driven by any single trait. A relationship between rs1799941 and SHBG levels, was also discovered, but it was dependent on MetS status. In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012), while in cases there was no association between rs1799941 and SHBG levels (p = 0.963).

Conclusions: The significant association between rs1799941 and MetS in children is not contingent on any single CM trait. Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children.

Show MeSH
Related in: MedlinePlus