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five\tletters\tand\twritten\tin\titalics.\tFor\tthe\nvast\tnumber\tof\tgenes,\thuman\tbeings\thave\ttwo\tcopies.\tTherefore\twhen\tdescribing\tthe\tgene\tand\nnucleotides\tpresent\t(whether\twild-type/usual\tor\tvariant/mutant)\tcertain\tconventions\tare\tused.\tIf\tthe\ntwo\tnucleotides\tare\twild-type,\tthe\tindividual\tis\tdescribed\tas\tbeing\thomozygous\twild-type.\tIf\tone\twild- | [
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type\tand\tone\tvariant\tare\tpresent,\tthe\tindividual\tis\theterozygous,\n\talso\tcalled\ta\t“carrier.”\tIf\tboth\nnucleotides\tare\tthe\tvariant\tnucleotide,\tthe\tindividual\tis\thomozygous\tvariant.\tWild-type\tand\tvariant\nstates\tmay\tbe\treferred\tto\tas\tthe\twild-type\tallele\tand\tthe\tvariant\tor\trisk\tallele,\twhich\tsimply\trefers\tto | [
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replaced\tby\ta\tT\t(thymidine)\tnucleotide\tat\tposition\t677\tin\tthe\t\nMTHFR\n\tgene\tsequence.\tIndividuals\nhomozygous\twild-type\thave\ta\tC\tat\tthis\tposition\tin\tboth\tcopies\tof\tthis\tgene.\tHeterozygotes\thave\t1\tC\nand\t1\tT\tand\tthose\thomozygous\tfor\n\tthe\tvariant\thave\ta\tT\tat\tthis\tposition\tin\tboth\tcopies\tof\tthe\tgene.\nAdditionally,\teach\tvariant\tis\tassigned\tan\t“\nrs\tnumber | [
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Additionally,\teach\tvariant\tis\tassigned\tan\t“\nrs\tnumber\n”\t(reference\tSNP\tcluster\tID).\tThe\tabove\nMTHFR\n\tvariant\tis\trs1801133.\tA\tdifferent\tvariant\twithin\tthis\tsame\tgene\tis\tthe\t\nMTHFR\n\tA1298C\tand\tis\nlabeled\trs1801131).\tThe\trs\tnumber\tis\tcritical\tbecause\tit\tdenotes\ta\tspecific\tlocation\twithin\tthe\tDNA\nand\tdifferent\tmutations\toften\tcreate\tdifferent | [
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variant\thas\tan\trs\tnumber.\nThe\tnext\tstep\tis\tto\ttake\tthe\tvariants\tidentified\tand\tmake\tpredictions\tas\tto\twhich\tvariants\tincrease\none’s\tsusceptibility\tto\tparticular\tdiseases\tand\tthen\tto\tselect\tappropriate\thealth-promoting\ninterventions\tfor\tthese\tsusceptibilities.\tMany\tgenomics\n\tresearchers\tand\thealth\tcare\tprofessionals | [
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particular\tvariant\tand\tthe\tstrength\tof\tits\tassociation\twith\tpromoting\n\tdisease\tand\tin\tthe\tefficacy\tof\nthe\trecommended\ttherapeutic\tintervention.\tBe\taware\tthat\tthe\tresearch\tinto\twhich\tvariants\tare\nstrongly\tassociated\twith\twhich\tdiseases\tis\tearly-stage.\tMany,\tmany\tvariants\thave\tbeen\tidentified\tbut | [
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few\texhibit\tboth\ta\tstrong\tassociation\tand\tprevalence\twithin\tmultiple\tpopulations.\tIn\tmost\tcases,\nmultiple\tgenes\tvariants,\tnot\ta\tsingle\tSNP,\tas\twell\tas\tspecific\tenvironmental\n\texposures\tare\tneeded\tfor\na\tdisease\tto\tdevelop.\tThe\tnutrition\tprofessional\twill\tneed\tto\tbe\table\tto\ttranslate\tthe\timplications\tof | [
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exposure.\tInterventions\tfocus\ton\tpreventing\tinflammation\tand\ton\tantiinflammatory\tapproaches\tto\nexisting\tinflammation.\tSee\t\nChapter\t7\n\tfor\ta\tcomprehensive\tdiscussion\tof\tinflammation,\tbiomarkers,\nand\tantiinflammatory\n\ttherapy.\nCommonly\tused\tgene\tvariants\tconsidered\tto\tincrease\tsusceptibility\tto\tan\tinflammatory\tstate\tare | [
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those\tassociated\twith\tinflammatory\tbiomarkers:\tC-reactive\tprotein\t(\nCRP\n),\tinterleukin-1beta\t(\nIL1ß\n),\ninterleukin-6\t(\nIL6\n),\tand\ttumor\tnecrosis\tfactor\talpha\t(\nTNF\n).\t\nCRP\n\tis\tproduced\tby\tthe\tliver\tin\tresponse\nto\tinflammation.\tInterleukin-1\tand\tinterleukin-6\tproteins\tare\tcytokines\tproduced\tas\tpart\tof\n\tthe | [
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the\ninflammatory\tprocess.\tThese\tproteins\tfunction\tas\tcell\tsignaling\tmolecules\tthat\tactivate\tthe\timmune\nsystem,\twhich\tinvolves\tinflammatory\tprocesses.\tInflammation\tis\ttypically\tself-limiting\tand\tabates\nwhen\tthe\tinfection\tor\tinjury\tis\tunder\tcontrol.\tIn\tthe\tcase\tof\tchronic\tdisease,\thowever,\tthe | [
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inflammatory\tresponse\tis\tessentially\tstuck\tin\tthe\t“on”\tposition.\nBiotransformation\t(detoxification)\nA\tparallel\tbetween\tpharmacogenomics\tand\tnutritional\tgenomics\tcan\tbe\tseen\twith\tthe\tphase\tI\tand\nphase\tII\tbiotransformation/detoxification\tpathways\tthat\tare\tactive\tin\tthe\tdigestive\ttract\tand\tliver.\tIn | [
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Subsequently,\tin\tPhase\tII\tglutathione-S-transferases\t(GSTs)\tand\tother\tenzymes\tadd\tchemical\tgroups\nto\tthe\tactivated\tmolecule\tto\trender\tit\tmore\tsoluble\tand\tless\ttoxic.\tKnowing\tthe\tgenomic\tstatus\tof\tthe\ngenes\tthat\tcode\tfor\tthese\tvarious\tenzymes\twould\tbe\thelpful\tfor\tpredicting\twhich\tnutritional\napproaches\twould\tbe\tbeneficial | [
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] |
approaches\twould\tbe\tbeneficial\n\tto\tsupport\tthe\tbiotransformation\tprocess\tand\twhen\tspecific\nmedications\tare\tused\t(see\t\nBox\t6.14\n).\nThe\tgene\tvariants\tcommonly\tfound\tin\tgenetic\ttest\tpanels\tthat\tinclude\tbiotransformation\tare\tfrom\nthe\tfamily\tof\t\nCYP\n\tgenes,\tthe\t\nGST\n\tgenes,\tand\ttwo\tsuper\toxide\tdismutase\t(\nSOD)\n\tgenes.\tOne\tor\tmore\tof\nthe\t\nCYP | [
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SOD)\n\tgenes.\tOne\tor\tmore\tof\nthe\t\nCYP\n\tgenes\ttypically\tinclude:\t\nCYP2D6,\tCYP2C19,\tCYP3A4,\tCYP1A2,\tCYP29,\tCYP2B6,\n\tand\nCYP2E1.\n\tThere\tare\tthree\n\tcommon\t\nGST\n\tvariants:\tGSTM,\tGSTP1,\tand\tGSTT1.\tThe\tSOD\tgenes\nrepresented\tare\t\nSOD1\n\t(copper-zinc\tSOD)\tand\t\nSOD2\n\t(manganese-dependent\tSOD)\tthat\tprotect | [
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oncogenes\t(tumor-promoting\tgenes)\tand\ttumor\tsuppressor\tgenes\tmust\tbe\tcarefully\torchestrated\tto\nmaintain\tnormal\tgrowth\tand\tdevelopment.\tOncogenes\tare\ttypically\tsilenced\n\tepigenetically\tand\ntumor\tsuppressor\tgenes\tare\tactivated.\tIf\teither\tof\tthese\tsystems\tmalfunction,\tthe\trisk\tfor\tcancer | [
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could\tbe\tincreased.\tAn\texample\twould\tbe\ta\tmethyl\tgroup\tattaching\tto\ta\ttumor\tsuppressor\tgene\tby\nmistake\tand\tturning\toff\tits\texpression.\tOr,\tif\tsomeone\tlacked\tsufficient\tfolate\tin\tthe\tdiet,\tan\noncogene\tmay\tnot\tbe\tsufficiently\tturned\toff.\nAlthough\ttotal\tpersonalization\tof\tcancer\ttherapy,\n\tor\tany\tother\tmedical\ttherapy,\tfor\tan\tindividual\tis | [
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this\tapproach\tis\trelatively\tnonspecific\tin\tthat\tit\n\ttargets\tboth\tcancerous\tand\tnoncancerous\tcells.\tOne\nof\tthe\tgoals\tof\tprecision\thealth\tis\tto\tharness\tthe\t“omic”\tdisciplines\tinto\tpersonalized\ttherapy\nappropriate\tfor\tindividuals\tand\ttheir\tparticular\ttype\tof\tcancer.\tThis\tapproach\trequires\tknowledge\tof | [
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the\tmolecular\tlandscape\tin\twhich\tthe\tcancer\texists\t(i.e.,\tthe\tperson’s\tgenomic\tand\tepigenomic\nmakeup\tand\tthe\tmolecular\tcharacteristics\tof\tthe\tcancer\titself).\n\tMolecular\tdefects\tin\tthe\tindividual’s\ngenome\tand\tepigenome,\tand\tin\tthe\tcancer\titself,\tcan\tprovide\tvaluable\tinformation\tabout\tpotential\ntherapeutic\ttargets.\tSee\t\nLuoh\tand\tFlaherty\t(2018) | [
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therapeutic\ttargets.\tSee\t\nLuoh\tand\tFlaherty\t(2018)\n\tfor\tan\toverview\tof\tthe\ttypes\tof\tcancers\tbeing\nstudied\tand\ttreated\tusing\tthis\tapproach.\nGene\tvariants\tand\tcancer\nWell-known\texamples\tof\tapplying\tgenomics\tto\tcancer\tinclude\tdetection\tof\tBRCA1\tand\tBRCA2\tgenes\nin\n\tdiagnosing\tbreast\tcancer\tand\tthe\thMLH1\tand\thMSH2\tgenes\tin\tdiagnosing\thereditary | [
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area\tof\tresearch\tbecause\ta\tsubstantial\tnumber\tof\thealth\tbenefits\thave\tbeen\treported\tfor\tthese\ncompounds.\tThe\tpolyphenol\tand\tglucosinolate\tcategories\tof\tphytonutrients\tare\tthe\tmost\tstudied\tfor\ncancer\ttreatment\n\tand\tprevention.\tEpigenetic\tchanges\tto\ttumor\tsuppressor\tgenes\tcan\tsilence\tthese\ngenes\tand\tlead\tto\tincreased\trisk\tof\ttumor\tdevelopment. | [
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genes\tand\tlead\tto\tincreased\trisk\tof\ttumor\tdevelopment.\nType\t2\tdiabetes\nType\t2\tdiabetes\tmellitus\t(T2DM)\tis\ta\tchronic\tdisorder\tthat\taccounts\tfor\tthe\tvast\tmajority\tof\nindividuals\twith\tdiabetes\t(see\t\nChapter\t29\n).\tT2DM\tis\tcomplex\tand\tresults\tfrom\tgene\tvariants\ninteracting\twith\tbioactive\tfood\tcomponents\tand\tother\tlifestyle | [
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interactions\tand\tmechanisms\tby\twhich\tthese\tinteractions\tepigenetically\tinfluence\tgene\texpression,\nwhich\twill\thelp\tin\tdeveloping\tnew\tand\teffective\tinterventions.\nGene\tvariants\tand\tT2DM\nA\tfew\trare\tmutations\thave\tbeen\tfound\tthat\tpredispose\tto\tT2DM,\tbut\n\tthey\tdo\tnot\texplain\tthe\thigh | [
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PPARG\n),\tadiponectin\n(\nADIPOQ\n),\tfat\tmass\tand\tobesity\tprotein/alpha-ketoglutarate\tdependent\tdioxygenase\t(\nFTO\n),\tclock\ncircadian\tregulator\t(\nCLOCK\n),\tand\tmelanocortin\t4\treceptor\t(\nMC4R\n).\t\nSLC30A8\n\tis\ta\tzinc\ttransporter\nthat\tis\trequired\tfor\tinsulin\tsynthesis\tand\tsecretion.\tThe\t\nADIPOQ,\tCLOCK,\tFTO,\n\tand\t\nMC4R\n\tvariants | [
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ADIPOQ,\tCLOCK,\tFTO,\n\tand\t\nMC4R\n\tvariants\nare\tassociated\twith\tobesity\tand\tincreased\trisk\tfor\tdeveloping\tT2DM.\t\nPPARG\n\tis\ta\ttranscription\tfactor\ninvolved\twith\tlipid\tmetabolism\tand\tadipocyte\tdifferentiation\tthat\tregulates\tthe\texpression\tof\tmultiple\ngenes.\tIt\thas\tbeen\timplicated\tin\tdiabetes,\tobesity,\tcancer,\tand\tatherosclerosis.\tFor\tfurther\tdepth | [
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into\nany\tof\tthese\tvariants,\tvisit\tthe\tGene\twebsite\tfrom\tthe\tNational\tCenter\tfor\tBiotechnology\tInformation\nor\tthe\tGenetics\tHome\tReference\twebsite\tfrom\tthe\tNational\tInstitutes\tof\tHealth.\nTCF7L2\n\tis\tinvolved\twith\tinsulin\tsecretion\tand\texhibits\tthe\tstrongest\tassociation\tby\tfar\twith\nsusceptibility\tto\tT2DM.\tThe\t\nTCF7L2 | [
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susceptibility\tto\tT2DM.\tThe\t\nTCF7L2\n\tgene\tencodes\ta\ttranscription\tfactor\tthat\tplays\ta\tkey\trole\tin\tthe\nWNT\tsignal\ttransduction\n\tpathway.\tFurther,\t\nTCF7L2\n\thas\tbeen\tdetected\tin\tmultiple\tpopulations.\tIn\nstudies\twith\tIndian\t(\nChandak\tet\tal,\t2007\n),\tChinese\tHan\t(\nDou\tet\tal,\t2013\n),\tJapanese\t(\nHorikoshi\tet\tal,\n2007\n),\tMexican\tAmerican\t( | [
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),\tJapanese\t(\nHorikoshi\tet\tal,\n2007\n),\tMexican\tAmerican\t(\nLehman\tet\tal,\t2007\n),\tAfrican\t(\nYako\tet\tal,\t2016\n),\tand\twhite\tEuropean\n(\nGroves\tet\tal,\t2006\n)\tpopulations,\tthe\tvariant\toccurred\tfrequently\tand\tincreased\tthe\trisk\tof\tT2DM\tby\n30%\tto\t50%.\t\nTCF7L2\n\thas\talso\tbeen\n\tfound\tto\tpredispose\tindividuals\twith\tmetabolic\tsyndrome\tto\ndeveloping\tT2DM\t( | [
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developing\tT2DM\t(\nKatsoulis\tet\tal,\t2018\n).\nEpigenetics\tand\tT2DM\nStudies\thave\tlong\tsuggested\tthat\tT2DM\tis\tstrongly\tassociated\twith\tdiet-and-lifestyle\tchoices,\tmost\nnotably\tfood\tchoices\t(especially\tdietary\tfat)\tand\texercise\thabits.\tT2DM\thas\tbeen\tassumed\tto\tbe\ngenetic\tin\torigin\tbut,\twith\tthe\texception\tof\t\nTCF7L2,\n\tthe\tlarge\tnumber\tof\tgene | [
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Nurses’\tHealth\tStudy\t(NHS)\tand\tits\tfollow-up\t(NHS\tII)\t(\nSun\tet\tal,\t2015\n),\tas\twell\tas\tthe\tHealth\nProfessionals\tFollow-Up\tStudy\t(\nWedick\tet\tal,\t2012\n),\tsuggest\n\tthat\tregular\tconsumption\tof\nphytonutrient-rich\tplant\tfoods\thelped\tlower\tthe\trisk\tof\tdeveloping\tT2DM. | [
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In\taddition\tto\tdiet\tand\texercise,\tother\tdaily\tlifestyle\tchoices\tinfluence\tthe\tphysiologic\timbalances\nthat\tlead\tto\tchronic\tinflammation\tand\tmust\tbe\tincorporated\tinto\tlifestyle\tchange\tprograms\tif\tthe\npositive\tchanges\tare\tto\tbe\tsustained\tlong\tterm.\tExamples\tinclude\tchronic\tpsychological\tand\nphysiological | [
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those\tat\trisk\tto\taddress\ttheir\tbarriers\tto\tmaking\thealthy\tlifestyle\tchoices.\nFor\tmore\tin-depth\tinformation\tabout\tthe\tgenomic\n\tand\tepigenetic\taspects\tof\tT2DM,\tsee\trecent\nreviews\tby\t\nSilveira\tet\tal\t(2019)\n,\t\nXue\tet\tal\t(2018)\n,\tand\t\nOrtega\tet\tal\t(2017)\n.\nObesity\nObesity\tis\tusually\tindicated\tby\tbody\tmass\tindex\t(BMI),\twhich\tis\tmeasured\tin\tkg/m\n2 | [
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2\n.\tIt\tis\timportant\tto\nassess\teach\tperson\tindividually,\tincluding\tweight\thistory,\twaist\tcircumference,\tand\tbody\tcomposition\nas\tpeople\twith\tlarger\tbody\tsizes\tcan\tbe\tmetabolically\thealthy\n\tin\tsome\tcases.\tDifferent\tcountries\tuse | [
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somewhat\tdifferent\tBMI\tscores\tto\tdefine\tobesity,\tbut\ta\tcommon\tglobal\tstandard\tis\tthat\tset\tby\tthe\nWorld\tHealth\tOrganization\t(WHO),\twhich\tclassifies\ta\tBMI\tof\t≥25\tkg/m\n2\n\tin\tadults\tas\noverweight/preobese,\ta\tBMI\t≥30\tkg/m\n2\n\tas\tobese,\tand\ta\tBMI\t≥40\tkg/m\n2\n\tas\textremely\tobese.\tWHO | [
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2\n\tas\tobese,\tand\ta\tBMI\t≥40\tkg/m\n2\n\tas\textremely\tobese.\tWHO\nhas\talso\tset\tBMI\tstandards\tfor\tchildren\tup\tto\t5\tyears\told\tand\t5\tto\t19\tyears\told.\tThe\tprevalence\n\tof\nobesity\tis\tsteadily\trising.\tIn\tthe\tUnited\tStates\tthe\t2015\tto\t2016\tNational\tHealth\tand\tNutrition\nExamination\tSurvey\tfound\t39.8%\tof\tadults\tand\t18.5%\tof\tyouth\tto\tbe\tobese\t(\nHales\tet\tal,\t2017\n). | [
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Hales\tet\tal,\t2017\n).\nIn\taddition\tto\tbeing\ta\tstorage\torgan\tready\tto\tprovide\tfor\tfuture\tenergy\tneeds,\tadipose\ttissue\tis\tan\nactive\tmetabolic\ttissue\tthat\tis\timportant\tin\twhole\tbody\tenergy\tbalance.\tAdipose\ttissue\tsecretes\nadipokines,\n\twhich\tare\tcell\tsignaling\tproteins.\tAdipokine\texamples\tinclude\tleptin,\tadiponectin,\tand | [
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stimulated\tthermogenesis.\n\tThe\tfoundational\twork\twas\tdone\tin\tmouse\tmodel\tsystems\tand\nsubsequently\tfound\tto\tbe\toperative\tin\thuman\tbeings\t(\nGhilardi\tet\tal,\t1996\n;\t\nDulloo\tet\tal,\t2002\n).\nAdiponectin\tis\ta\tprotein\thormone\tadipokine\tencoded\tby\tthe\t\nADIPOQ\n\tgene\tand\tproduced\tby | [
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ADIPOQ\n\tgene\tand\tproduced\tby\nadipocytes.\tIt\tappears\tto\tbe\timportant\tfor\tmetabolic\tbalance,\tparticularly\tin\treference\tto\tthe\tinsulin\nresistance,\toxidative\tstress,\tand\tchronic\tinflammation\n\tcharacteristic\tof\tthe\tmetabolic\tsyndrome\n(\nAchari\tand\tJain,\t2017\n).\tIn\tparticular\tthe\tbalance\tbetween\tadiponectin\tand\tleptin\thas\tbeen | [
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).\tIn\tparticular\tthe\tbalance\tbetween\tadiponectin\tand\tleptin\thas\tbeen\ncorrelated\twith\tthe\tobesity\tcomponent\tof\tmetabolic\tsyndrome.\tA\tdecrease\tin\tthe\tadiponectin/leptin\nratio\tincreases\tthe\trisk\tof\tobesity,\tinflammation,\tand\tdevelopment\tof\tthe\tmetabolic\tsyndrome\n(\nFrühbeck\tet\tal,\t2017\n).\nADIPOQ\n\tis\ta\tgene\tof\tinterest\tbecause\tof\tits\tassociation | [
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).\nADIPOQ\n\tis\ta\tgene\tof\tinterest\tbecause\tof\tits\tassociation\n\twith\tobesity\tbut\talso\tpotentially\tfor\ttype\t2\ndiabetes\tand\tmetabolic\tsyndrome.\tOne\tof\tthe\tSNPs\tin\tthis\tgene\t(-11391G>A,\trs17300539)\tappears\nto\tlink\tincreased\tlevels\tof\tadiponectin\twith\tdecreased\trisk\tof\tobesity.\tIn\twhite\tAmericans,\tthose\twith | [
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one\tor\tmore\tcopies\tof\tthe\tvariant\tallele\t(A)\thad\televated\tadiponectin\tlevels\tand\tdecreased\tweight,\nwaist\tand\thip\tcircumference,\tand\tBMI\t(\nWarodomwichit\tet\tal,\t2009\n).\tThese\tresearchers\tfurther\ndetected\ta\tgene-diet\tinteraction\tbetween\tthe\tvariant\tallele\t(A)\tand\tmonounsaturated\tfat\t(MUFA). | [
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] |
When\tMUFA\tintake\twas\tequal\tto\tor\tgreater\tthan\t13%\tof\ttotal\tenergy,\tthose\twith\tone\tor\tmore\tcopies\nof\tthe\tA\tallele\t(AA\tor\tAG\tgenotype)\thad\ta\tlower\tBMI\tcompared\twith\tindividuals\twith\tthe\tGG\ngenotype\t(2\tcopies\tof\tthe\tnon-variant\tG\tallele).\tNo\teffect\tof\tthe\tA\tallele\twas\tseen\n\tfor\twaist | [
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] |
for\twaist\ncircumference,\tinsulin\tresistance\tor\tfor\tsaturated\tfat\tor\tpolyunsaturated\tfats.\tOther\tresearchers\nhave\treported\tincreased\trisk\tof\tobesity\tin\tthe\tpresence\tof\tSNPs\tin\t\nADIPOQ\n\tin\tthe\tNorth\tIndian\nPunjabi\tpopulation\t(\nKaur\tet\tal.,\t2018\n)\tand\tin\tthe\tTunisian\tpopulation\t(\nZayani\tet\tal,\t2018\n).\tThese\ninteresting\tfindings\twith\t\nADIPOQ | [
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Zayani\tet\tal,\t2018\n).\tThese\ninteresting\tfindings\twith\t\nADIPOQ\n\twill\tlikely\tcontinue\tto\tbe\tstudied\tin\tmultiple\tpopulations\tand\n\tunder\nvarying\tdietary\tconditions.\nAs\twith\tleptin,\tmuch\tof\tthe\tinitial\twork\twith\tadiponectin\thas\tbeen\tcarried\tout\tusing\tmouse\tmodel | [
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obesity\tacross\tmultiple\npopulations.\tAdditionally,\tthe\tcomplexity\tof\tobesity\tand\tthe\tmultitude\tof\tmolecules\tinvolved\thas\nmade\tit\tchallenging\tto\tuntangle\tthe\tmultiple\tinteractions\tthat\tincrease\tor\tdecrease\trisk\tof\ndeveloping\tobesity\t(\nJagannadham\tet\tal,\t2016\n).\tA\trecent\treview\tby\t\nUnamuno\tet\tal\t(2018)\n\tprovides | [
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and\thow\n\thumans\tbecome\tobese\tis\tmultifaceted\tand\tmultiple\tdisciplines\twill\tbe\tinvolved\tin\tdefining\nthe\tmechanisms\tand\tfinding\teffective\tsolutions.\tThe\taddition\tof\tcontemporary\tneuroscience\tand\nbehavioral\tresearch\tto\tthe\tsearch\tfor\tanswers\tas\tto\twhy\tand\thow\twe\tbecome\tobese\tis\texpanding\tour\ninsight\tinto\tthis\tchallenging\tdilemma\t(see\t\nChapter\t20\n). | [
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insight\tinto\tthis\tchallenging\tdilemma\t(see\t\nChapter\t20\n).\nThe\tsections\tthat\tfollow\thighlight\tgenes\tand\tgene\tvariants\n\tthat\tare\tamong\tthose\twith\ta\tstronger\nassociation\twith\tobesity\tthan\tmost\tvariants,\talong\twith\ta\tdiscussion\tof\tthe\trole\tof\tepigenetics\tin\nobesity.\tThe\tfact\tthat\tenvironmental\tfactors\tplay\ta\tmajor\trole\tin\ttriggering\tthe\tdevelopment\tof | [
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on\tshifting\tone’s\thealth\ttrajectory\tfrom\tdisease\tsusceptibility\tto\thealth\tand\tvitality.\nGene\tvariants\tand\tobesity\nIn\tterms\tof\tits\tgenetic\tbasis,\tobesity\thas\tbeen\tcategorized\tas\tboth\tmonogenic\tand\tpolygenic.\nMonogenic\t(single\tgene)\tobesity\thas\thistorically\treferred\tto\tthose\n\tgenes\tthat,\twhen\tmutated,\tlead\tto | [
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genes\tthat,\twhen\tmutated,\tlead\tto\nsevere\tobesity.\tExamples\tof\twell-studied\tgene\tvariants\tassociated\twith\tmonogenic\tobesity\tinclude\nmutations\tin\t\nMC4R\n\t(melanocortin-4\treceptor),\t\nLEP\n,\tand\t\nLEPR.\n\tIn\tcontrast,\t\npolygenic\n\t(multigene)\nobesity\thas\tbeen\treferred\tto\tas\t“common\tobesity”\twhere\tmultiple\tgenes\tand\tenvironmental\ttriggers | [
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are\tinvolved.\tThis\tbasis\tfor\tobesity\toccurs\tfrequently.\tIn\tcommon\tobesity,\n\tmutation\tin\ta\tsingle\tgene\ncontributes\tonly\ta\tsmall\tdegree\tof\trisk;\tdevelopment\tof\tthe\tsusceptibility\tto\tbecoming\tobese\tis\nstrongly\tdependent\ton\tthe\tinteraction\twith\tenvironmental\ttriggers.\tHowever,\tthe\trecent\tfinding\tby\nFairbrother\tet\tal\t(2018)\n\tthat\tmutations\tin\t\nMC4R | [
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Fairbrother\tet\tal\t(2018)\n\tthat\tmutations\tin\t\nMC4R\n\tare\tfound\tfrequently\tin\tobese\tindividuals\tin\tthe\ngeneral\tpopulation\tmakes\tthis\ttype\tof\tall\tor\tnothing\tcategorization\tquestionable.\n\tThis\trevelation\tis\nnot\tsurprising\tgiven\tthat\tmost,\tif\tnot\tall,\tgene-function-disease\tassociations\tare\tbeing\tfound\tto | [
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constitute\ta\tcontinuum\tof\tphenotypes\tranging\tfrom\tsilent\tto\tmild\tto\tsevere\teffects\ton\tfunction.\nHowever,\tbe\taware\tthat\tthis\ttype\tof\tclassification\tis\tin\tthe\tliterature\tand\tcan\tcause\tconfusion.\tIn\tthis\nsection\tthe\tfocus\twill\tbe\ton\twhat\thas,\tto\tdate,\tbeen\ttermed\tcommon\tobesity\tinvolving\n\tmultiple\tgenes\nand\tmultiple\tenvironmental\ttriggers. | [
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dioxygenase).\tIts\tmechanism\tof\taction\tappears\tto\tbe\trelated\tto\tthe\tregulation\tof\tadipose\ttissue\ndevelopment,\twhich\tsuggests\tbody\tcomposition\tis\taffected\t(\nYang\tet\tal,\t2017\n).\tVariations\tin\tthe\t\nFTO\ngene\thave\tbeen\tfound\tin\tmultiple\tpopulations.\tIts\teffect\n\tis\tgreater\tin\tEuropean\tdescendants\tthan\tin\nAfrican\tor\tAsian\tpopulations\t(\nLoos\tand\tYeo,\t2014 | [
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Lappalainen\tand\tcolleagues\t(2012)\n\tinvestigated\tthe\teffect\tof\tthis\nsame\tSNP\ton\tBMI\tin\tsubjects\tin\tthe\tFinnish\tDiabetes\tPrevention\tStudy.\tThis\tgroup\talso\tfound\nelevated\tBMI\tvalues\tin\tthose\tconsuming\ta\thigh-fat\tdiet.\tMore\trecently\t\nVimaleswaran\tet\tal\t(2016)\nreported\ta\tgene–diet\tinteraction\tin\ta\tsecond\t\nFTO | [
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] |
inhibits\tcytokine\tsignal\ttransduction\t(part\tof\tthe\tinflammatory\nresponse)\tthrough\tthe\tJanus\tkinase/signal\ttransducer\tand\tactivator\tof\ttranscription\t(JAK/STAT)\nsignaling\tpathway.\t\nSOCS3\n\tis\tfrequently\toverexpressed\tin\tobesity\tand\tdiabetes\t(\nGalic\tet\tal,\t2014\n).\tIn\nan\t\nexpression\tgenome-wide\tassociation\tstudy\t(eGWAS)\n,\t\nXu\tet\tal\t(2018) | [
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] |
expression\tgenome-wide\tassociation\tstudy\t(eGWAS)\n,\t\nXu\tet\tal\t(2018)\n\tfound\tthat\tthe\t\nSOCS3\npromoter\twas\thypomethylated\tin\tobese\tindividuals.\tWithin\tthis\tlow-methylated\t\nSOCS3\n\tgroup,\tthose\nwho\thad\thad\tfive\tor\tmore\tmajorly\tstressful\tlife\tevents\twere\tat\tincreased\trisk\tof\tobesity.\nThe\t\nPPARG | [
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The\t\nPPARG\n\tgene\tis\ta\tnuclear\treceptor\tthat\tfunctions\tas\ta\ttranscription\tfactor\tand\tis\ta\tkey\ncontributor\tto\tfat\tcell\tformation.\tIt\tis\tfrequently\treferred\tto\tas\tthe\t“master\tregulator”\n\tof\nadipogenesis\tand\tdifferentiation\t(\nMukherjee\tet\tal,\t1997\n).\tGene–diet\tinteractions\tfor\tthe\tPPARG\tgene\nhave\tbeen\treported,\toriginally\tby\t\nMemisoglu\tet\tal\t(2003) | [
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have\tbeen\treported,\toriginally\tby\t\nMemisoglu\tet\tal\t(2003)\n\tand\tmore\trecently\tby\t\nRodrigues\tand\ncolleagues\t(2017)\n.\tIn\ta\tsubgroup\tof\tthe\tNurses’\tHealth\tStudy,\tMemisoglu\tand\tcolleagues\ninvestigated\tthe\tinteraction\tbetween\tthe\t\nPPARG2\n\tPro12Ala\tSNP\t(the\tPro\tallele\tis\tthe\twild-type\tallele\nand\tthe\tAla\tallele | [
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] |
and\tthe\tAla\tallele\n\tthe\tvariant\tallele)\tand\tdietary\tfat\tintake.\tThose\twith\tthe\tPro/Pro\tgenotype\twho\talso\nhad\tthe\thighest\tdietary\tfat\tintake\thad\tsignificantly\thigher\tBMI\tvalues\tthan\tthose\twho\thad\tthe\tlowest\ndietary\tfat\tintake.\tThere\tdid\tnot\tappear\tto\tbe\ta\tgene–diet\tinteraction\twith\tthe\tAla\tallele\twith\trespect\nto\tBMI.\t\nRodrigues\tet\tal\t(2018) | [
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to\tBMI.\t\nRodrigues\tet\tal\t(2018)\n\treported\ton\tseverely\tobese\tindividuals\tand\tfound\tthat\tthose\twith\tone\nor\tmore\n\tcopies\tof\tthe\tAla\tallele\thad\thigher\tBMI\tvalues\tand\thigher\tpolyunsaturated\tfat\tintake.\tIt\tis\nnot\tunusual\tto\tencounter\tthese\ttypes\tof\tinconsistencies\tas\tresearchers\tattempt\tto\tidentify\tSNPs\tthat | [
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