This was an exploratory study reporting two novel findings. First, genotypes at two SNPs in the CD36
gene, rs1761667 and rs1527483, were associated with oral fat perception. At rs1761667, African Americans who had the A/A genotype perceived Italian salad dressings to be creamier than did G/A and G/G individuals, regardless of how much fat was actually in the salad dressing. This relationship was independent of age, sex, and reported intake of Italian salad dressing in the diet. Second, rs1761667 genotype was also associated with reported acceptance of added fats and oils, a group of foods which includes cooking oils, spreads, and full-fat salad dressings. African Americans who carried the A/A genotype at this site reported greater liking of added fats and oils when compared to G/A, but not G/G individuals, according to Sheffé post hoc
analysis. However, average liking ratings by G/A and G/G individuals were not significantly different from one another, so it is possible that in a larger cohort, an effect might have been seen with G/G individuals as well. This relationship was independent of not only BMI, but also cognitive attempts to control food intake. The fact that CD36
showed a stronger relationship to liking of added fats than to high-fat foods in general is interesting because the former group consists of foods that are predominantly composed of triglycerides, such as butter, margarine, and cooking oils. Although fatty acid composition, processing, and source of the oil (34
), can influence the overall flavor of these fats, their predominant sensory property is “fatty.” If CD36
is involved with development of fatty acid and triglyceride preferences as shown in animals (24
), we might expect a stronger association between variation in the gene and reported liking of fats and oils than for more complex high-fat foods that provide other sensory qualities like sweetness (e.g., cookies) or saltiness (e.g., potato chips). Alternatively, most added fats and oils are fluids, and studies have demonstrated that it is easier to perceive fat in this physical form than in solid foods (35
). The possibility that CD36
may be a gene target associated with fat intake, through a mechanism of oral fat perception and preference, warrants additional investigation.
Although it is not possible to draw firm conclusions, some speculation as to why A/A individuals like added fats and oils more than G/A and G/G individuals can be made from close examination of the sensory data collected in this study. Although A/A individuals do not appear to discriminate that accurately between salad dressings that range in fat content from 5 to 55% as evidenced by nearly identical perceived fat and creaminess ratings given across the three samples, they perceive the samples to be creamier than do individuals who have other genotypes at this allele. Creaminess is a complex sensory characteristic that consists of both flavor and textural components (14
), but overall, it is perceived as a positive attribute of foods that contain fat. In studies that have collected data on both perceived creaminess and liking, there is generally a positive relationship between the two. Most of these studies have examined relationships in ice creams (36
), or other fluid dairy products (38
), however, it is not known if the same relationship exists for oil-based salad dressings. Further complicating this relationship, “creaminess” can be used by consumers to describe both flavor and textural aspects of foods, so identifying the source of variation in this attribute can be difficult. The notion that A/A individuals may like added fats and oils because they perceive them to be creamier is a question that warrants further study. This is especially important because, as in the present study, creaminess can be achieved not only with fat, but also by increasing emulsifiers such as carrageenan. Given that fatty acids are ligands for CD36, it is possible that differences in perceived creaminess ratings between different genotype groups are due to differences in the ability to detect small amounts of free fatty acids in the samples, and as a result, textural attributes like creaminess become more pronounced. Additional studies are needed to confirm this.
The rs1761667 polymorphism that was associated with both oral fat perception and reported fat acceptance in the current study is in the promoter region of the CD36
gene. In whites, G is the minor allele, whereas in African Americans, A is the minor allele. In the present study, the CD36
variant that best predicted oral fat perception and acceptance (rs1761667) occurred at high frequency, with the homozygous “at risk” genotype (A/A) present in about 20% of individuals. These findings suggest that variation in CD36
may represent an important marker for fat perception and acceptance in African Americans, and the impact this may have on metabolic health risks should be further investigated. Ma et al.
) analyzed identical SNPs to those studied here and found that Italian males with the G/G genotype had higher free fatty acids and triglyceride levels. Similarly, Madden et al.
) published findings in a small, nonhomogeneous cohort from the UK and demonstrated that G/G individuals were also less likely to show improvements in plasma triacylglycerol levels after a fish oil rich dietary intervention when compared to G/A and A/A individuals. The totality of available evidence suggests that presence of the A/A genotype at rs1761667 may reduce CD36 protein expression and, because of this, confer postingestive benefits on lipid metabolism. The fact that we demonstrated that African Americans with the A/A genotype showed higher preferences for added fats and oils, a dietary behavior that can be associated with increased, not decreased health risk, may suggest that our findings are due to linkage disequilibrium between this and another SNP that was not genotyped. The linkage disequilibrium may differ between whites and African Americans and thus account for the difference in allelic association. Alternatively, because fat preferences are affected by both oral and postoral responses to this nutrient, it is possible that differential postoral responses to fat between A/A vs. G/A & G/G individuals may be mediating this effect. It should be noted, however, that the lipid profiles of the individuals in this study were not tested, and future studies are needed to clarify the relationship between variation at rs1761667 and cardiovascular health in African Americans.
A secondary aim of this study tested the association between 5 CD36
SNPs and adiposity. Presence of the minor allele at rs1527483 was associated with both increased perceived ratings of fat content in Italian salad dressings and decreased BMI, although the latter relationship was only a trend. Stewart et al. (40
) recently published data that showed an inverse relationship between oral fatty acid sensitivity and BMI. Participants who were classified as “hypersensitive” to oleic acid had lower BMIs than those classified as “hyposensitive.” Previously, we reported a similar relationship from this cohort; African Americans who were poor at discriminating differences in the fat content of salad dressings had higher BMIs than those who were able to discriminate fat content more accurately (41
). In the present study, ratings of perceived fat content in the salad dressing were included in the model as a covariate and this reduced the P
value of the relationship between rs1527483 genotype and BMI from P
= 0.05 to P
= 0.11. In multiple linear regression models that were run as exploratory analyses, perceived fat content ratings of the 35% and 55% fat salad dressings explained ~15% of the total variance in BMI, whereas rs1527483 genotype explained only 11%. However, BMI did not change the significance of the relationship between rs1527483 genotype and perceived fat content when it was included in the model. Taken together with findings from Stewart et al. (40
), we speculate that the rs1527483 genotype may impact body weight in part by impacting oral fat perception. An increased oral sensitivity to the fat content of the diet may help consumers detect small changes in fat intake, and as a result, they may be less likely to consume excess amounts of this nutrient. These findings are preliminary and need to be confirmed in larger cohorts.
We also identified another SNP associated with obesity in this cohort that has not been identified previously, rs3840546. Several recent reports have shown relationships between CD36
polymorphisms and BMI in European adolescents (42
) European adults, (43
) and Korean adults (44
), but not all reports have been consistent (45
). This is the first study to report an association between rs3840546 and obesity in an African-American population. The mechanisms that mediate the effects of CD36 on body weight are not known, but differences in the metabolic availability of fatty acids for storage vs. oxidation in “at risk” individuals is one possibility (46
). In our study, individuals who had a deletion at rs3840546 had mean BMIs that were over 30 kg/m2
, which is associated with significant health risks (47
). In addition, carrying a deletion at rs3840546 was also associated with increased waist circumference, of significance because the presence of increased abdominal adiposity is associated with greater morbidity than elevated BMI alone (48
). One important caveat to mention is that our cohort was small, consisting of only 25 heterozygous (I/Ds) and 2 homozygous (D/D) for the “at risk” genotype. Testing the impact of this SNP on body weight in larger cohorts is necessary to confirm these findings.
The present study had several limitations. First, it was conducted in African Americans, a single ethnicity group. It is unclear if these results will generalize to other ethnic groups. Second, fat preferences were self-reported, and these measures have well-known biases (49
). In addition, we did not collect fat liking measures in response to the Italian salad dressings used for sensory testing and doing so could have shed additional light on the relationship between oral fat perception and acceptance. Moreover, for a genetic association study, our sample was small and results are not corrected for multiple testing. There is a debate about the extent to which correction for multiple testing should be applied in exploratory studies (50
). Still, results should be interpreted with caution and confirmation studies are needed. Further, an association study is not able to verify the functional significance of these polymorphisms, but is only able to identify regions of the gene that might warrant more rigorous follow-up investigations.
The fatty acid translocase, CD36, has a range of functions in multiple tissues, including recent studies in animals that report an important role in fat preferences. This study provides preliminary evidence that CD36 is involved with oral fat perception and liking of added fats and oils in humans. In addition, we found associations between variation at the CD36 gene and adiposity. At present, these findings suggest that perception and preference for some dietary fats may be in part explained by common heritable variation in African Americans. If these findings are supported by future investigations, the CD36 genotype may be a useful genetic marker of excess fat consumption in an environment in which these foods are plentiful.