many genes partially responsibleor the development o chronicdisease have been suggested, andsome have been confrmed. Amongthese, perhaps the most well knownare the oncogenes. Oncogenes aregenes which code or proteins thatcontrol cell death, or apoptosis; orwhich control cell division and pro-lieration (Croce, 2008). Rapid cellprolieration or inhibition o apop-tosis may cause a cell to becomecancerous, and begin the growth o lesions which may, in turn, becometumors. Which mechanism causesthe onset o cancer is dependenton the specifc oncogene and tissuetype involved (Land et al., 1983).Another chronic disease withvast implications or public healthis cardiovascular disease. Common biochemical markers or elevatedcardiovascular risk include nonspecifcindices o systemic inammation, andtheir elevation is associated with car-diovascular risk, although they may beelevated due to more acute conditionssuch as inection. It has been dem-onstrated that the circulating levelso these markers may be inuenced,at least in part, by various geneticactors (Pankow et al., 2001). Othergenetic actors have also shown aneect in regulating the overall energy balance o an individual, contribut-ing to the degree o one’s obesity orleanness (Barsh et al., 2000). Thesefndings may inuence how cardio-vascular disease risk is diagnosed.Hyperinsulinemia and diabetesare examples o chronic conditionsplaguing the general public whichhave their origins, or partial ori-gins, in genetics. Deective geneticregulation o several proteins whichrespond to the presence o insulinmay be implicated in the etiologyo type 2 diabetes. Ducluzeau et al.(2001) ound decreased expressiono key proteins and their mRNAin type 2 diabetic patients, andobserved a lack o response to thepresence o insulin by up-regulationo key response proteins. This lack o response is linked to deective expres-sion o the genes or these proteins inresponse to insulin. Type 1 diabetesis reliant on genetic components toa greater degree than type 2 diabe-tes because the genetic regulationo type 1 diabetes is polygenic, oraccomplished by several genes.
Nutrient Regulation of Gene Expression
In some cases, intake or levels o specifc nutrients have been shownto directly impact gene expres-sion. Oten, this occurs by meanso transcription actors. Tran-scription actors are biochemicalentities which bind to the DNAand either promote or inhibittranscription o genes. Severalnutrients are known to bind totranscription actors and regulategene expression in this manner(Muller and Kersten, 2003).The regulation o gene tran-scription by atty acids is perhapsthe best understood o the nutri-ent gene-regulation pathways. Amajor pathway by which atty acidsmodulate gene expression is theperoxisome prolierator-activatedreceptors (PPARs), which activategene transcription when atty acids bind to them (Bouwens et al.,2007). One such receptor has beenshown to activate genes respon-sible or utilization o atty acidsor energy (Kresten et al., 1999).Circulating atty acid concentrationsare increased during asting. Theseasting-induced amplifed atty acidconcentrations increase the expres-sion o several genes involved in
-oxidation o atty acids (Bouwenset al., 2007). One o the isoormso PPAR is PPAR
, which is anuclear receptor that binds to thepromoters o genes whose prod-ucts avor atty acid breakdown(Madrazo and Kelly, 2008). How-ever, these receptors need activatorsto realize their ull potential. Fattyacids can act as ligands to PPAR
,such as oleic acid, to enhance activ-ity (Michaud and Renier, 2009).Furthermore, the PPARs do not act by themselves but require anotherpartner, the retinoic acid receptorswith cis-retinoic acid as a ligand.Thus, atty acid catabolism is some-what dependent upon cis-retinoicacid or any other nutrient or drugthat enhances the activity o the nuclear receptors (Figure 2).Also, PPAR activity activationmay lead to weight loss (Verrethet al., 2004). However, much has been done in developing drugs toact as ligands to both PPAR
*Source: American Heart Assoc.** Source: Centers for Disease Control and Prevention
P o p u l a t i o n i n M i l l i o n s
Figure 1. Prevalence of chronic diseases and related states in the United States (2006).