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The role of a FADS1 polymorphism in the association of fatty acid blood levels, BMI and blood pressure in young children : analyses based on path models

(2017) PLOS ONE. 12(7).
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Abstract
Background : The recent obesity epidemic in children also showed an increase in the prevalence of hypertension. As blood pressure (BP) is associated with (long-chain) polyunsaturated fatty acids (LC PUFA), genetic variation in desaturase enzymes being involved in the synthesis of LC PUFA may be associated with BP. This study aimed to investigate the direct effects (independent of mediating variables) and indirect effects (mediated through intermediate variables) of a common variant in the FADS1 gene, rs174546, known to affect delta-5 desaturase (D5D) activity on PUFA level, body mass index (BMI) and BP. Methods : A subsample of the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) baseline survey including 520 children aged 2 to <10 years from six European countries was included. The association between rs174546 (T<C) and BP z-score as well as the mediating effects of selected key PUFA levels (dihomo-gamma-linolenic acid, DGLA; arachidonic acid, ARA; eicosapentaenoic acid, EPA) or estimated D5D activity (D5D index) and BMI z-score were investigated through path model analyses, adjusting for sex, age, educational level of parents, family history of hypertension, lifestyle factors and blood levels of saturated and monounsaturated fatty acids, triglycerides and low density lipoprotein cholesterol. Whole blood fatty acids were measured by a validated gas chromatographic method and recorded as percentage of weight of all fatty acids detected. Results : Minor allele carriers of the SNP rs174546 had significantly higher DGLA and lower ARA and EPA levels as well as a lower D5D index. Via ARA and BMI z-score, the polymorphism had an indirect lowering effect on systolic BP z-score for each additional T allele (standardized effect estimate -0.057, p = 0.007). For DGLA, EPA and D5D index, the indirect effects of rs174546 on systolic BP were also negative but did not reach significance. DGLA and EPA had an increasing indirect effect on systolic BP via BMI. Results for diastolic BP were in general similar but effect estimates were lower compared to systolic BP. Conclusion : Genetic variation in FADS1 influences BP via ARA and BMI indicating a favorable effect of the minor allele in SNP rs174546. Thus, polymorphisms with an impact on the D5D activity may play a role for the BP level mediated through PUFA and BMI. Therefore, health effects of dietary n-6 and n-3 PUFA may vary depending on genetic FADS1 variants.
Keywords
GENOME-WIDE ASSOCIATION, CARDIOVASCULAR RISK-FACTORS, GENE-CLUSTER, WHOLE-BLOOD, DESATURASE ACTIVITIES, REFERENCE VALUES, QUALITY-CONTROL, ADIPOSE-TISSUE, PLASMA, ADOLESCENTS

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Citation

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Chicago
Wolters, Maike, Carmen Dering, Alfonso Siani, Paola Russo, Jaakko Kaprio, Patrizia Risé, Luis A Moreno, et al. 2017. “The Role of a FADS1 Polymorphism in the Association of Fatty Acid Blood Levels, BMI and Blood Pressure in Young Children : Analyses Based on Path Models.” Plos One 12 (7).
APA
Wolters, Maike, Dering, C., Siani, A., Russo, P., Kaprio, J., Risé, P., Moreno, L. A., et al. (2017). The role of a FADS1 polymorphism in the association of fatty acid blood levels, BMI and blood pressure in young children : analyses based on path models. PLOS ONE, 12(7).
Vancouver
1.
Wolters M, Dering C, Siani A, Russo P, Kaprio J, Risé P, et al. The role of a FADS1 polymorphism in the association of fatty acid blood levels, BMI and blood pressure in young children : analyses based on path models. PLOS ONE. 2017;12(7).
MLA
Wolters, Maike, Carmen Dering, Alfonso Siani, et al. “The Role of a FADS1 Polymorphism in the Association of Fatty Acid Blood Levels, BMI and Blood Pressure in Young Children : Analyses Based on Path Models.” PLOS ONE 12.7 (2017): n. pag. Print.
@article{8538800,
  abstract     = {Background : The recent obesity epidemic in children also showed an increase in the prevalence of hypertension. As blood pressure (BP) is associated with (long-chain) polyunsaturated fatty acids (LC PUFA), genetic variation in desaturase enzymes being involved in the synthesis of LC PUFA may be associated with BP. This study aimed to investigate the direct effects (independent of mediating variables) and indirect effects (mediated through intermediate variables) of a common variant in the FADS1 gene, rs174546, known to affect delta-5 desaturase (D5D) activity on PUFA level, body mass index (BMI) and BP. 
Methods : A subsample of the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) baseline survey including 520 children aged 2 to {\textlangle}10 years from six European countries was included. The association between rs174546 (T{\textlangle}C) and BP z-score as well as the mediating effects of selected key PUFA levels (dihomo-gamma-linolenic acid, DGLA; arachidonic acid, ARA; eicosapentaenoic acid, EPA) or estimated D5D activity (D5D index) and BMI z-score were investigated through path model analyses, adjusting for sex, age, educational level of parents, family history of hypertension, lifestyle factors and blood levels of saturated and monounsaturated fatty acids, triglycerides and low density lipoprotein cholesterol. Whole blood fatty acids were measured by a validated gas chromatographic method and recorded as percentage of weight of all fatty acids detected. 
Results : Minor allele carriers of the SNP rs174546 had significantly higher DGLA and lower ARA and EPA levels as well as a lower D5D index. Via ARA and BMI z-score, the polymorphism had an indirect lowering effect on systolic BP z-score for each additional T allele (standardized effect estimate -0.057, p = 0.007). For DGLA, EPA and D5D index, the indirect effects of rs174546 on systolic BP were also negative but did not reach significance. DGLA and EPA had an increasing indirect effect on systolic BP via BMI. Results for diastolic BP were in general similar but effect estimates were lower compared to systolic BP. 
Conclusion : Genetic variation in FADS1 influences BP via ARA and BMI indicating a favorable effect of the minor allele in SNP rs174546. Thus, polymorphisms with an impact on the D5D activity may play a role for the BP level mediated through PUFA and BMI. Therefore, health effects of dietary n-6 and n-3 PUFA may vary depending on genetic FADS1 variants.},
  articleno    = {e0181485},
  author       = {Wolters, Maike and Dering, Carmen and Siani, Alfonso and Russo, Paola and Kaprio, Jaakko and Ris{\'e}, Patrizia and Moreno, Luis A and De Henauw, Stefaan and Mehlig, Kirsten and Veidebaum, Toomas and Moln{\'a}r, Den{\'e}s and Tornaritis, Michael and Iacoviello, Licia and Pitsiladis, Yannis and Galli, Claudio and Foraita, Ronja and B{\"o}rnhorst, Claudia},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  language     = {eng},
  number       = {7},
  pages        = {17},
  title        = {The role of a FADS1 polymorphism in the association of fatty acid blood levels, BMI and blood pressure in young children : analyses based on path models},
  url          = {http://dx.doi.org/10.1371/journal.pone.0181485},
  volume       = {12},
  year         = {2017},
}

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