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

Abstract

BackgroundThe 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.MethodsA 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.ResultsMinor 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.ConclusionGenetic 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.

Lipid ratios representing SCD1, FADS1, and FADS2 activities as candidate biomarkers of early growth and adiposity

“…Our findings on lipid ratios potentially related to SCD1, FADS1 and FADS2 activities are in line with recent human studies that have associated polyunsaturated fatty acids (PUFA) intake and the related enzyme activities, SCD1, FADS1, and FADS2, with childhood metabolic parameters [22] . For example, Wolters et al reported that a FADS1 polymorphism influenced blood pressure and body mass index (BMI) in a multinational European study involving children aged 2-10 years [23] . Another study from the same group reported positive associations between fatty acid ratios representing SCD1 and FADS2 activities at baseline with BMI and TG levels both at baseline and 2 years later [24] .…”

Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,★,★★

“…A distinct FADS haplotype defined by 28 SNPs is associated with an enhanced ability to biosynthesize HUFA [107] . FADS SNPs are associated with maternal, infant, and child health phenotypes, for instance, plasma lipids in infants [108] , gestational duration [109] , perinatal depression [110] , attention/hyperactivity and learning [ 111 , 112 ], cognition and intelligence [ 113 , 114 ] and blood pressure in young children [115] . A recent study showed mothers who were heterozygous or homozygous for the minor alleles of FADS1 and FADS2 SNPs had infants with a greater head circumference and birth weight [116] .…”

Interaction of Dietary Linoleic Acid and α-Linolenic Acids with rs174547 in FADS1 Gene on Metabolic Syndrome Components among Vegetarians

“…Besides, the insignificant association could also be due to the discrepancy in respondents’ characteristics. Notably, the past study that had successfully uncovered the association of genetic variation with BP and FBG was focused on young children whose age ranged from 2 to 10 years old [29]. However, the age of the respondents from this former study was much lower as compared to the average mean age of the vegetarians in the present study (48.3 years old).…”

“…Little is known about the associations of rs174547 in FADS1 gene with other MetS components, such as BP and FBG. Considering that BP and FBG are associated with LC-PUFAs level in the bloodstream [27,28,29], the interaction of rs174547 in FADS1 gene with LA and ALA intakes may also be associated with BP and FBG levels. Furthermore, the dietary patterns of respondents from these existing studies were not reported [19,24,25,26], whereby it is possible that the respondents may have consisted of both vegetarians and non-vegetarians.…”