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FADS haplotype

From SNPedia


Based on papers published in 2011 and 2012, two haplotypes are thought to represent the majority of individuals over a particular chromosomal block spanning the FADS1 and a portion of the FADS2 gene; these haplotypes are known as FADS haplotype-D and -A.[PMID 23028684OA-icon.png];[PMID 22503634OA-icon.png]

The FADS1 and FADS2 genes fatty acid desaturases, rate-limiting proteins converting linoleic acid (LA) and α-linolenic acid (ALA) short chain (SC) polyunsaturated fatty acids (PUFAs) found primarily in vegetable oils into arachidonic acid (AA), and docosahexaenoic acid (DHA), long-chain (LC) PUFAs important in human neuronal, metabolic, and inflammatory development and found primarily in foods derived from animals (such as fish, eggs and animal fats). Although the science is complex and only beginning to be understood, an overview of the current consensus follows.

FADS Haplotype Definition: The haplotypes were originally defined based on 28 tightly-linked (and thus usually co-inherited) SNPs spanning the FADS1/FADS2 region. SNP rs174537 is one of the original 28 and is numerous DTC chips, so it's a reasonable representative for the haplotype; rs174537(G) tags the FADS-D haplotype, and rs174537(T) tags the FADS-A haplotype.[PMID 22503634OA-icon.png]

The Evolutionary View: apes and Neanderthals are primarily FADS-haplotype A. Haplotype D first appeared after the split from Neanderthals (around 500,000 years ago) but prior to the exodus of modern humans from Africa (50,000–100,000 years ago). At that time (the exodus of our ancestors) both haplotype A and haplotype D were probably present in Africa and therefore both are present in European, Asian, and Oceanian populations. The low frequency of haplotype D in current Native American populations indicates that haplotype D might have been lost due to a colonization bottleneck.[PMID 22503634OA-icon.png]

Metabolism: Individuals with the FADS-D haplotype convert the SC-PUFA precursors (ALA and LA) to their LC counterparts (DHA and AA) at a higher rate than the those with FADS-A haplotypes (and D/A heterozygotes are intermediate). This higher conversion rate means that on average FADS-D individuals have higher lipid levels than FADS-A individuals. The magnitude of the change does not appear to be that dramatic, but may have medical significance; in one study, FADS D/D homozygotes had 24% higher DHA levels and 43% higher AA levels than FADS A/A homozygotes.[PMID 22503634OA-icon.png]

Ethnic differences: Currently, the primary populations with high FADS-A haplotype frequency are those of Native American and/or South American origin. Highest FADS-D haplotypes are found in African populations, where there are almost no FADS-A individuals, whereas in most European/Caucasian, Asian and Oceanic populations there is very roughly a 2:1 ratio between the FADS D:A haplotypes. However, it is also clear that variants other than those defining the FADS-D and -A haplotypes have (also) been subject to selective pressure; for example, the insertion variant of rs66698963 in South Asian, African, and some East Asian populations leads to higher LC-PUFA levels and may imply an adaptive advantage for this variant in populations with traditionally more vegetarian diets.[PMID 27188529OA-icon.png] Conversely, two FADS2 variants ([[rs7115739 and rs174570), are associated with decreased concentrations of LC-PUFAs but increased concentrations of SC-PUFAs in Inuits from Greenland, apparently compensating for a diet quite low in SC-PUFAs while quite high in LC-PUFA intake from fish and other marine mammals.[PMID 26383953]

Dietary Implications: While the FADS-D haplotype may have evolved in response to the development of agriculture, the 'modern western diet' and associated cooking oils are associated with a three-fold increase in dietary levels of the omega-6 and polyunsaturated fatty acid (PUFA) linoleic acid (LA). These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations. While it appears clear that dietary recommendations should ultimately take genetic factors into account, at this time the interactions are insufficiently defined.[PMID 24853887OA-icon.png],[PMID 24977108OA-icon.png]