**6. Magnitude of the response**

Because of the heterogeneity in the type and duration of the interventions described the magnitude of the lipid response to dietary interventions varied widely: in one study the change in LDL cholesterol in the Apo B *Eco*RI *R*-*R*- genotype group was as large as 59% of the baseline concentration. In the studies that showed a significant difference in response between genotype groups, the results also varied widely: in some studies, the difference in response between 2 genotype groups was ≈20% of the baseline lipid concentration (Rantala et al., 2000; Clitfon., 1997). However, the magnitude of these differences cannot be estimated with any accuracy, largely because most studies had only a small number of subjects in the rare genotype group (Masson et al, 2003). The proportion of variance in the lipid response

Nutrigenetics and Dyslipidemia 65

reexamined after the availability of new information from genotype analyses. Therefore, it is perhaps not surprising that significant effects were not found in many studies because the numbers of individuals in each genotype group were so small. In many studies there were too few subjects homozygous for the rare allele to allow an analysis that would take into account differences in the response between heterozygote's and homozygote's. For Apo E, where there are 6 possible genotypes, differences in the grouping of these could also lead to differences in results between studies. This illustrates that meta-analyses are important because they can detect effects with greater power and greater precision because of their inflated sample size (Rantala et al., 2000; Lopez-Miranda et al., 1994). In addition, in studies with small sample sizes, genotype misclassification of one individual may significantly affect the interpretation and validity of the results. Conflicting results may also occur because of the different dietary protocols that were followed. The studies reviewed varied widely in the composition and length of the baseline and experimental diets. The dietary factors responsible for the changes seen in each genotype group are not clear because many studies modified several dietary factors, and so the dietary content in future studies should be tightly controlled and compliance must be strictly measured not only for cholesterol and the amount and type of fatty acids but also for other influential dietary components such as fiber and plant sterols. In addition, these studies investigated fasting lipid and lipoprotein concentrations; however, the effect of genetic variation may be more evident in the postprandial state than in the less-common fasting state). Differences in the age, sex, body mass index, menopausal status, dietary backgrounds, and baseline lipid values of the participants could also have contributed to the discrepancies between the results. For instance, subjects with the E4 allele tend to have higher baseline total and LDL-cholesterol concentrations, and so greater responses in these subjects could reflect the regression to the mean phenomenon. It is also possible that weight change could account for differences in lipid and lipoprotein changes. In addition, a significant effect may not reflect a causal relation but the allele may be in linkage disequilibrium with another one that does. For example, the base change that results in the *Xba* I site in the gene for Apo B does not alter the amino acid, and so it may be in linkage disequilibrium with another functional mutation

The studies varied widely in terms of the number and type of study participants, the composition and duration of the dietary interventions, the nutrients studied and dietary assessment methods used in the observational studies, and the polymorphisms analyzed some of which had not been studied before with regard to the lipid response to diet (Masson

Evidence suggests that genetic variation may contribute to the heterogeneity in lipid responsiveness. At present, the evidence is limited but suggestive and justifies the need for future studies with much larger sample sizes based on power calculations, with carefully controlled dietary interventions, and that investigate the effects of polymorphisms in multiple genes rather than in single genes. Investigating gene-diet interactions will increase our knowledge of the mechanisms involved in lipid metabolism and improve our understanding of the role of diet in reducing cardiovascular disease risk

(Masson et al., 2003).

et al., 2005).

**10. Conclusion** 

(Masson et al., 2003).

attributable to a single polymorphism is not likely to be > 10% (Xu et sal., 1990). Therefore, individual genes contribute only a small part to the variation in the lipid response; however, when several genes are considered, the proportion of variance explained could be larger (Masson et al, 2003).
