Abstract
Fatty acid desaturase 1 (FADS1) gene controls the fatty acid metabolism pathway in the human body. The lower intake of α-linolenic acid (ALA) than linoleic acid (LA) among vegetarians may disrupt the fatty acid metabolism and limit the conversion of ALA to anti-inflammatory products such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This cross-sectional study aimed to determine the interaction of rs174547 in FADS1 gene with LA and ALA on metabolic syndrome (MetS) components. A total of 200 Chinese and Indian vegetarians in Kuala Lumpur and Selangor, Malaysia participated in the present study. The data on socio-demographic characteristics, vegetarianism practices, dietary practices, anthropometric measurements, blood pressure (BP), and overnight venous fasting blood samples were collected from the vegetarians. The rs174547 in FADS1 gene was significantly associated with MetS and its components such as waist circumference (WC) and fasting blood glucose (FBG). Multiple logistic regression analyses revealed that vegetarians with TT genotype of rs174547 in FADS1 gene had higher odds for MetS, larger WC, higher BP, and a lower level of HDL-c. Two-way ANOVA analysis showed that LA interacts with rs174547 in FADS1 gene to affect HDL-c (p < 0.05) among vegetarians. The present findings suggest the need to develop dietary guidelines for vegetarians in Malaysia. Prospective studies are also needed to affirm the interaction between LA and rs174547 in FADS1 gene on HDL-c among Malaysian vegetarians.
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Key Points
In comparison to those who practice non-vegetarian diet, the consumption of α-linolenic acid (ALA) among vegetarians is relatively low, as compared to linoleic acid (LA). ALA and LA are two precursors of essential fatty acids, that needs to be obtained from our daily diet, which can alter the enzyme activities of delta-5 desaturase (D5D) and delta-6 desaturase (D6D). D5D and D6D are two important rate limiting enzymes in the endogenous synthesis of long chain polyunsaturated fatty acids (LC-PUFAs).
Over the past two decades, several genomic-wide association studies (GWAS) have reported the association of rs174547 in FADS1 gene with MetS components as well as its interaction with LA and ALA on MetS components among the general population. The rs174547 is a single nucleotide polymorphism (SNP) of the FADS1 gene. Based on the findings from a previous study, LA interacts with rs174547 in FADS1 gene, which affects WC and HDL-c level among the general population. Further, ALA interacts with rs174547 in FADS1 gene to modify the level of HDL-c among the general population. The extent of the influences of gene-diet interaction on MetS components, specifically in the vegetarian population, remains unknown. In addition, vegetarians have a different LC-PUFAs profile than non-vegetarians. Non-vegetarians who consume meat have significantly higher LC-PUFAs intakes, but lower n-6:n-3 intake ratios than vegetarians. This cross-sectional study aimed to determine the association of rs174547 in FADS1 gene with MetS and its components as well as the interaction between LA and ALA intakes and rs174547 in FADS1 gene on MetS components among Malaysian vegetarians.
This study reported the association of rs174547 in FADS1 gene with MetS among Malaysian vegetarians. In the present study, TT genotype of rs174547 had the highest frequency (39.5%), followed by CT genotype (32.0%) and CC genotype (28.5%) in FADS1 gene. In relation to LA and ALA, the present study found that percent of total energy (%) for LA (4.1%) and ALA (0.3%) met the recommended intakes for LA (3.0 to 7.0%) and ALA (0.3–1.2%). However, the daily intake of LA and ALA were lower than the dietary reference intake (DRI) for Americans.
The present study found that vegetarians with TT genotype of rs174547 in FADS1 gene had a higher number of MetS components, and a higher prevalence of MetS than vegetarians with CC and CT genotypes in bivariate analysis. The logistic regression analysis also revealed that vegetarians with TT genotype of rs174547 in FADS1 gene had higher odds (OR: 3.57 95% CI: 1.02-12.47) of developing MetS than vegetarians with CC genotype of rs174547 in FADS1 gene after adjusting for age, sex, and ethnicity. These results indicated that TT genotype of rs174547 in FADS1 gene could be a possible risk factor for MetS among Malaysian vegetarians. To date, there are no published data on the association between rs174547 in FADS1 gene and MetS among vegetarians, which makes the direct comparison impossible. In terms of WC, about one in three vegetarians (35.5%) had large WC, with a higher prevalence of large WC found among vegetarians with TT genotype of rs174547 in FADS1 gene. The logistic regression analysis in the present study found that vegetarians with TT genotype had higher odds (OR: 4.73, 95% CI: 1.41–15.93) of developing large WC than vegetarians with CC genotype, after adjusting for age, sex, and ethnicity. These findings suggest that the TT genotype of rs174547 in FADS1 gene could be a risk genotype for large WC among vegetarians.
The present study found that the dietary intake levels of LA may modify the association between rs174547 in FADS1 gene and HDL-c among vegetarians. The interaction of dietary LA intake with rs174547 in FADS1 gene on HDL-c may be explained by the decrease in FADS1 activity among vegetarians with TT genotype of rs174547 and high LA intake, which may promote the accumulation of LA that subsequently inhibits the production of n-3 PUFAs. This may reduce the HDL-c raising effect among those individuals with TT genotype of rs174547 and high LA intake, and contribute to reduced HDL-c. In other words, over-consumption of LA may inhibit the production of n-3 PUFAs, which reduces HDL-c level among those with TT genotype of rs174547 in FADS1 gene.
The rs174547 of FADS1 gene was significantly associated with MetS and its components such as WC and FBG. Vegetarians with TT genotype of the rs174547in FADS1 gene had higher odds of developing MetS, larger WC, higher BP, and lower level of HDL-c. Further investigations are needed in order to determine the possible linking mechanism between TT genotype of rs174547 in FADS1 gene with MetS and its components. Meanwhile, the present study suggests that the dietary intake of LA may interact with rs174547 in FADS1 gene to affect HDL-c level, which warrants the needs to monitor the amount of dietary LA intakes in vegetarians’ daily diet. In terms of policy, the present study suggests the need to develop dietary guidelines for vegetarians in Malaysia, and emphasized the balanced intakes of LA and ALA intake. Currently, several countries such as North America and Japan have developed specific dietary guidelines for vegetarians. Prospective studies such as cohort studies on gene-diet interaction are suggested in order to affirm the interaction between LA and rs174547 in FADS1 gene on HDL-c among Malaysian vegetarians.