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SNP JOURNAL
A reference ebook for the
FOUNDATIONS IN NUTRIGENOMICS course

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WELCOME TO THE SNP JOURNAL

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Welcome to the SNP JOURNAL

The SNP JOURNAL ebook has been developed to provide you with clear
and concise information on the SNPs you will most commonly encounter in
commercial nutrigenetic tests. The list of SNPs is by no means comprehensive,
but is an excellent place to start. The SNP JOURNAL provides an easy to use

WELCOME TO THE SNP JOURNAL


reference ebook for the course, as well as for clinical practice.

In the Table of Contents the SNPs have been divided into the three modules
of the Foundations course, where you will encounter them. By clicking on the
name of the SNP you will be taken to the relevant page.

For each SNP we have provided you with the following information:

An overview of the gene Impact of SNP on biological pathway/s


Full name of the gene Nutrient interaction
Symbol of the gene Established diet-gene interactions
Nucleotide/base change Potential dietary recommendations
Amino acid change References
(where appropriate)
Population frequencies

In addition, you will be able to make notes alongside each SNP as you proceed
through the course and SNP JOURNAL. You will be able to save these notes
and edit them, as you proceed, making the SNP JOURNAL, - YOUR SNP
JOURNAL. A working document for your growing knowledge.

The SNP JOURNAL will also be available for purchase as a printed book,
should you work better that way.
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TABLE OF CONTENTS

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1 ANGIOTENSIN 1 CONVERTING ENZYME (ACE)


INSERTION/DELETION 6

ANGIOTENSINOGEN (AGT) -6 G>A 8

CYTOCHROME P450 1A2 (CYP1A2 A>C) 12

HUMAN LEUKOCYTE ANTIGEN (HLA) GENE HAPLOTYPE 16

HEMOCHROMATOSIS GENE (C282Y and H63D) 20

LACTASE (LCT) 13910 C>T (or MCM6) 24

FATTY ACID DESATURASE (FADS) 592 G>T RS174537 28


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2 CYTOCHROME P450 1B1 (CYP 1B1) 1294 C>G VAL432LEU 32


TABLE OF CONTENTS

CYTOCHROME P450 1A1 (CYP1A1) Ile462Val A>G and 6235 T>C 36

CATECHOL-O-METHYLTRANSFERASE (COMT) G>A VAL158MET 40

GLUTATHIONE S-TRANSFERASES (GSTM1, GSTT1 and GSTP1) 44

APOLIPROTEIN A5 (APOA5) -1131 T > C 48

APOLIPOPROTEIN C3 (APOC3) 3175 C>G 52

APOLIPOPROTEIN E (APOE) ARG-CYS 112 and 158 (E2, E3, E4) 56

QUINONE REDUCTASE (NQO1) 609 C>T 62

CYSTATHIONINE -SYNTHASE (CBS) 699 C>T 66

TRANSCRIPTION FACTOR 7-LIKE 2 GENE


(TCF7L2) IVS3 C>T 70

SOLUTE CARRIER FAMILY 2 (SLC2A2)


OR GLUT2 THR110ILE C>T 74

CHOLESTERYL ESTER TRANSFER PROTEIN


(CETP) TAQ1B 279 G>A 78

LIPOPROTEIN LIPASE (LPL) 1595 C>G S447X 82


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2 METHYLENETETRAHYDROFOLATE REDUCTASE
(MTHFR) 1298 A>C 86

5-METHYLTETRAHYDROFOLATE-HOMOCYSTEINE
METHYLTRANSFERASE (MTR) 2756 A>G 90

METHIONINE SYNTHASE REDUCTASE (MTRR) 66 A>G 94

APOLIPOPROTEIN A-1 (APOA1) -75 G>A 98

ENDOTHELIAL NITRIC OXIDE SYNTHASE (ENOS3)


GLU298ASP G>T 102

HEPATIC LIPASE (LIPC or HL) -514 C>T 106

METHYLENETETRAHYDROFOLATE REDUCTASE

TABLE OF CONTENTS
(MTHFR) 677 C>T 110

MANGANESE SUPEROXIDE DISMUTASE


(SOD2 or MNSOD) V16A or 47 T>C 114
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3 BETA2-ADRENERGIC RECEPTOR GENE (ADRB2)


ARG16GLY A>G, GLN27GLU C>G 118

3-ADRENERGIC RECEPTOR (ADRB3) TRP64ARG T>C 122

APOLIPOPROTEIN A2 (APOA2) -492 T>C 126

DOPAMINE RECEPTER D2 (DRD2) TAQ1A C>T 130

FATTY ACID BINDING PROTEIN (FABP2) ALA54THR G>A 134

FAT MASS AND OBESITY ASSOCIATED GENE (FTO) T>A 138

MELANOCORTIN 4 RECEPTOR (MC4R) T>C 142

PERILIPIN (PLIN1) 11482 G>A 146

PEROXISOME-PROLIFERATOR ACTIVATED RECEPTOR


GAMMA (PPARG) C>G PRO12ALA 150

TUMOR NECROSIS FACTOR ALPHA GENE (TNFA) -308 G>A 154

INTERLEUKIN-6 (IL-6) -174 G>C 158

CIRCADIAN LOCOMOTOR OUTPUT CYCLES KAPUT


(CLOCK) 3111 T>C 162
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ANGIOTENSIN 1 CONVERTING ENZYME (ACE)
INSERTION/DELETION

Overview Salt sensitivity is estimated to be present in 51% of hypertensive


and 26% of normotensive populations. The ACE gene codes for the
angiotensin-converting enzyme and is part of the renin-angiotensin
ANGIOTENSIN 1 CONVERTING ENZYME (ACE) INSERTION/DELETION

system, which controls blood pressure by regulating the volume of


fluids in the body.

Name of gene Angiotensin 1 converting enzyme (ACE) gene

Symbol of gene ACE

rs number rs4646994

Base change The presence or absence (insertion or deletion) of the enzyme is


based on a 287 bp Alu repeat element in the gene

Population Frequency Non-hispanic whites DD=28.8%, ID=51%, II=19.6%

Non-hispanic black DD=33.8%, ID=49.8%, II=16.4%

Mexican American DD=20.7%, ID=51.9%, II=27.4%

Impact of SNP on Levels of circulating enzyme are associated with the presence or
absence of the (rs4646994 ) 287 bp Alu repeat in this gene. The
biological pathway/s
deletion means there is no enzyme activity.

Nutrient interaction Sodium

Established diet-gene Meneton et al. found that the prevalence of salt sensitive
hypertension in those with the II genotype and ID genotype were
interactions
significantly higher than DD genotype.

Zhang et al. found that in individuals with the ID+II genotype,


hypertension was increased by a high salt intake, while in the DD
genotype it was not. The interaction was more prominent in the
overweight group than in the non-overweight group.

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ANGIOTENSIN 1 CONVERTING ENZYME (ACE)
INSERTION/DELETION

Potential dietary In those patients with hypertension and with the ID or II genotype, aim
to eat no more than 2,300 milligrams (approximately 1 level teaspoon
recommendations
of salt) of sodium per day.

ANGIOTENSIN 1 CONVERTING ENZYME (ACE) INSERTION/DELETION


References Armando, I., Villar, V., & Jose, P. (2015). Genomics and
pharmacogenomics of salt-sensitive hypertension. Current
hypertension reviews.

Hunt, S. C., Cook, N. R., Oberman, A., Cutler, J. A., Hennekens, C. H.,
Allender, P. S., . . . Williams, R. R. (1998). Angiotensinogen genotype,
sodium reduction, weight loss, and prevention of hypertension:
trials of hypertension prevention, phase II. Hypertension, 32(3),
393-401.

http://www.nutritionfoundation.org.nz/nutrition-facts/minerals/
sodium

Notes

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ANGIOTENSINOGEN (AGT) -6 G>A

Overview The angiotensinogen gene has been linked to essential hypertension


and increased blood pressure. A functional AGT gene variant has
been associated with hypertension and has been shown to affect
blood pressure response to sodium and weight reduction, and the
development of hypertension.

Name of gene Angiotensinogen (AGT) gene

Symbol of gene AGT

rs number rs5051. The AGT -6 G>A is in full linkage disequilibrium with the rs699,
often written as M235T
ANGIOTENSINOGEN (AGT) -6 G>A

Base change G>A

Population Frequency European GG=21.7%, GA=65.2%, AA=13%

African American GG=4.2%, GA=25%, AA=70.8%

Asian GG=7%, GA=41.9%, AA=51.2%

Impact of SNP on The AGT -6 G>A gene variant has been demonstrated to be functional
and is believed to contribute towards hypertension susceptibility. The
biological pathway/s
A allele alters the binding of a nuclear protein, resulting in increased
gene transcription compatible with increased angiotensinogen levels.

Nutrient interaction Sodium

Established diet-gene Hunt et al. reported that AA genotype individuals develop hypertension
to a greater degree than those with the other genotypes when there
interactions
is no intervention, they also respond more favorably to salt reduction
and/or weight loss intervention. Whereas the GG genotype group
may comprise primarily salt-insensitive individuals.

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ANGIOTENSINOGEN (AGT) -6 G>A

Potential dietary In those patients with hypertension, and with the AA genotype, aim to
eat no more than 2,300 milligrams (approximately 1 level teaspoon of
recommendations
salt) of sodium per day. Weight loss should also be encouraged where
appropriate.

References Armando, I., Villar, V., & Jose, P. (2015). Genomics and
pharmacogenomics of salt-sensitive hypertension. Current
hypertension reviews.

Hunt, S. C., Cook, N. R., Oberman, A., Cutler, J. A., Hennekens, C. H.,
Allender, P. S., . . . Williams, R. R. (1998). Angiotensinogen genotype,
sodium reduction, weight loss, and prevention of hypertension:
trials of hypertension prevention, phase II. Hypertension, 32(3),

ANGIOTENSINOGEN (AGT) -6 G>A


393-401.

Norat, T., Bowman, R., Luben, R., Welch, A., Khaw, K. T., Wareham,
N., & Bingham, S. (2008). Blood pressure and interactions between
the angiotensin polymorphism AGT M235T and sodium intake: a
cross-sectional population study. Am J Clin Nutr, 88(2), 392-397.
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ANGIOTENSINOGEN (AGT) -6 G>A

Notes
ANGIOTENSINOGEN (AGT) -6 G>A

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ANGIOTENSINOGEN (AGT) -6 G>A

Notes

ANGIOTENSINOGEN (AGT) -6 G>A

SAVE YOUR NOTE RESET YOUR NOTE


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CYTOCHROME P450 1A2 (CYP1A2 A>C)

Overview Twin studies reveal that genetics plays a role in individual variability in
caffeine consumption as well as in the direct effects of caffeine. At low
doses, caffeine effects include mild euphoria, alertness, and enhanced
cognitive performance, but at higher doses, it can produce nausea,
anxiety, trembling, and jitteriness. Caffeine is metabolized primarily by
the CYP1A2 enzyme. and accounts for approximately 95% of caffeine
metabolism. The clearance of caffeine can vary to up to 40-fold within
and between individuals.

Name of gene Cytochrome P450 1A2


CYTOCHROME P450 1A2 (CYP1A2 A>C)

Symbol of gene CYP1A2

rs number rs762551

Base change A>C

Population Frequency European AA=54.2%; AC=33.3%; CC=12.5%

African American AA=26.1%; AC=56.5%; CC=17.4%

Asian AA=41.7%; AC=54.2%; CC=4.2%

Impact of SNP on The occurrence of the CYP1A2 C allelle leads to a decreased enzyme
inducibility, resulting in impaired caffeine metabolism.
biological pathway/s

Nutrient interaction Caffeine

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CYTOCHROME P450 1A2 (CYP1A2 A>C)

Established diet-gene Individuals who are homozygous for the CYP1A2 A allele (AA
genotype) are rapid caffeine metabolizers, whereas carriers of
interactions
the variant CYP1A2 C allelle are slow caffeine metabolizers (AC
and CC genotypes).

Cornelis et al. reported that increased coffee intake is associated


with an increased risk of non-fatal MI, but only among individuals
with the slow C allele.

Palatini et al. demonstrated that carriers of the slow A allele are


at increased risk of hypertension.

CYTOCHROME P450 1A2 (CYP1A2 A>C)


Potential dietary For the general population it is recommended to drink coffee or
caffeine containing products in moderation. I.e. consuming 3-4 cups
recommendations
(300-400 mg) of coffee per day. Slow metabolizers may do better
restricting coffee to less than 2 cups of coffee per day and monitoring
their overall caffeine intake.

References De Caterina R, El-Sohemy A. Moving towards Specific Nutrigenetic


Recommendation Algorithms: Caffeine, Genetic Variation and
Cardiovascular Risk. Journal of nutrigenetics and nutrigenomics.
2016;9(2-4):106-115

Cornelis, M. C., El-Sohemy, A., Kabagambe, E. K., & Campos,


H. (2006). Coffee, CYP1A2 genotype, and risk of myocardial
infarction. JAMA, 295(10), 1135-1141. doi: 10.1001/jama.295.10.1135

Palatini, P., Ceolotto, G., Ragazzo, F., Dorigatti, F., Saladini, F.,
Papparella, I., . . . Santonastaso, M. (2009). CYP1A2 genotype
modifies the association between coffee intake and the risk of
hypertension. Journal of hypertension, 27(8), 1594-1601.

Yang, A., Palmer, A. A., & de Wit, H. (2010). Genetics of caffeine


consumption and responses to caffeine. Psychopharmacology,
211(3), 245-257.
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CYTOCHROME P450 1A2 (CYP1A2 A>C)

Notes
CYTOCHROME P450 1A2 (CYP1A2 A>C)

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CYTOCHROME P450 1A2 (CYP1A2 A>C)

Notes

CYTOCHROME P450 1A2 (CYP1A2 A>C)

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Gene-Based Personalised Health and Nutrition


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