Mino a ian o s 16827043 in he i on egula o
hemoju elin gene (HJV) con ibu es o
hype ension
The TAMRISK s udy
Seppo T. Nikka i, MD, PhD
a,b
, Anni-Lau a Vis o, MD
a
, Ki si M. Mää ä, MD
a
, Ta ja A. Kunnas, PhD
a,∗
Abs ac
I is known ha i on o e load may lead o an inc eased isk o many diseases. Acco ding o GWAS s udies, i on egula o y p o ein
HFE gene a ian H63D ( s1799945) was associa ed wi h hype ension, an obse a ion which we we e able o confi m also in ou
TAMRISK coho . Thus, i is possible ha abno mali ies in i on homeos asis may p edispose o hype ension. This p omp ed us o
s udy whe he he e is an associa ion be ween hype ension and ano he i on o e load-associa ed gene, hemoju elin (HJV), which
has 2 common polymo phic si es ( s 16827043, s7536827).
The s udy included 336 hype ensi e cases and 480 con ols. All pa icipan s we e 50- yea -old Finnish men and women, and he
da a was collec ed om he Tampe e adul popula ion ca dio ascula isk s udy (TAMRISK). Geno ypes we e de e mined using
Compe i i e Allelic Specific PCR (KASP).
We ound ha he mino a ian o he HJV polymo phic si e s16827043 (G-allele) is a s a is ically significan ac o associa ed wi h
hype ension among 50 yea -old indi iduals compa ed wi h he AA geno ype ca ie s (OR=1.66, 95% CI: 1.06 –2.60, P=0.03). The
isk was e en highe when o e weigh subjec s (BMI>30) we e excluded om he analyses. Fo he o he polymo phic a ian
s7536827, associa ion wi h hype ension was ound only among no mal o sligh ly o e weigh A-allele ca ie s.
In conclusion, HJV gene ic a ian s we e associa ed wi h essen ial hype ension in Finnish subjec s om he TAMRISK coho .
P e ious s udies oge he wi h he p esen one indica e ha indi iduals wi h possible dys egula ion o i on me abolism may ha e
highe isk o hype ension han hose wi h no mal i on homeos asis.
Abb e ia ions: BMI =body mass index, CI =confidence in e al, HFE =his ocompa ibili y complex class I-like ansmemb ane
p o ein (hemoch oma osis p o ein), HJV =hemoju elin (p e iously HFE2), PCR =polyme ase chain eac ion, PHE =pe iodic heal h
examina ion.
Keywo ds: gene ic a ian s, HJV, hype ension, i on
1. In oduc ion
I on me abolism has been s udied ex ensi ely o unde s and how
he body main ains i on homeos asis. I is now known ha
hepcidin plays an impo an ole on in es inal i on abso p ion
and i on ecycling in mac ophages. Hepcidin unc ions by
dec easing he amoun o i on eleased om mac ophages o
abso bed om in es ine. I is also known ha hepcidin defiency
may lead o se e e i on o e load in mul iple o gans.
[1–4]
Hepcidin
syn hesis is complexly egula ed by di e en p o eins and
pa hways.
[5]
Two impo an ansmemb ane p o eins, HFE
(his ocompa ibili y complex class I-like ansmemb ane p o ein)
and HJV (hemoju elin), a e key modula o s o hepcidin
exp ession. HJV ac s as a bone-mo phogene ic p o ein (BMP)
co- ep esso , d i ing hepcidin ansc ip ion ia he BMP-SMAD
signaling cascade.
[6]
Using a mouse model, Ken e al
[7]
showed
ha HFE and HJV ope a e in he same pa hway o egula ion o
hepcidin exp ession and i on me abolism. Recen ly, Wu e al
[8]
showed ha HJV is he key egula o o hepcidin and ha HFE
ac s in an HJV-dependen manne . Some mu a ions in hese 2
p o eins ha e been associa ed wi h se e e i on o e load in
pa ien s wi h he edi a y haemoch oma osis.
[9,10]
Dys egula ion in i on homeos asis may also lead o mild i on
o e load, which has no been gene ally aken in o accoun . Two
p e ious GWAS s udies
[11,12]
ha e ound an associa ion be ween
HFE (H63D) gene ic a ian and hype ension. We we e able o
eplica e his associa ion in he TAMRISK coho and showed
ha ca ie s o he mu a ion had highe isk o hype ension
han hose wi hou his mu a ion.
[13]
Mu a ions in he HJV gene ha lead o se e e i on o e load a e
a e, al hough o e 40 mu a ions o HJV ha e been ecog-
nized.
[14]
The e o e, we analyzed 2 ela i ely equen a ian s o
his gene ha ha e been shown o media e dys unc ional i on
Edi o : Ming Zhang.
Funding: Compe i i e esea ch unding o he Pi kanmaa Hospi al Dis ic unded
his wo k.
The au ho s ha e no conflic s o in e es o disclose.
a
Depa men o Medical Biochemis y, Facul y o Medicine and Li e Sciences,
Uni e si y o Tampe e, Finland,
b
Fimlab labo a o ies, Tampe e, Finland.
∗
Co espondence: Ta ja A. Kunnas, Depa men o Medical Biochemis y, Facul y
o Medicine and Li e Sciences, Uni e si y o Tampe e, Finland
(e-mail: a ja.kunnas@u a.fi).
Copy igh ©2017 he Au ho (s). Published by Wol e s Kluwe Heal h, Inc.
This is an open access a icle dis ibu ed unde he e ms o he C ea i e
Commons A ibu ion-Non Comme cial-No De i a i es License 4.0 (CCBY-NC-
ND), whe e i is pe missible o download and sha e he wo k p o ided i is
p ope ly ci ed. The wo k canno be changed in any way o used comme cially
wi hou pe mission om he jou nal.
Medicine (2017) 96:5(e6052)
Recei ed: 22 Augus 2016 / Recei ed in final o m: 23 Decembe 2016 /
Accep ed: 13 Janua y 2017
h p://dx.doi.o g/10.1097/MD.0000000000006052
Obse a ional S udy Medicine®
OPEN
1
egula ion.
[15]
In he p esen s udy, we wan ed o examine a
possible associa ion be ween hese HJV gene ic a ian s and
hype ension in he Finnish TAMRISK coho .
2. Ma e ials and me hods
2.1. S udy popula ion
The Tampe e adul popula ion ca dio ascula isk s udy (TAM-
RISK) is a p ospec i e, longi udinal popula ion-based heal h su ey
s udy in Tampe e, a ci y in sou he n Finland wi h a popula ion o
210 000. The da a o he TAMRISK s udy was collec ed om he
pe iodic heal h examina ions (PHE) done o 50-yea -old men and
women li ing in Tampe e. The PHEincluded one 60-minu e session
wi h a public heal h nu se a he cen e ’s heal h examina ion uni as
p e iously desc ibed.
[13,16]
TAMRISK da a includes in o ma ion o
isk ac o s o hype ension: blood p essu e, weigh , amily his o y
o ca dio ascula diseases, lipid alues and smoking, diabe es, and
exe cise habi s. Physical ac i i y was defined as imes o exe cise/
week (enhanced b ea hing and swea ing). Cu en and p e ious
diseases we e iden ified based on sel - epo o diagnosis by a
physician, including hype ension. Cases in his s udy we e he
subjec s who had hype ension and/o CAD a he age o 50 yea s as
diagnosed by a physician by no mal heal hca e p ocedu es. Fo
mos pa ien s, physicians diagnose hype ension when blood
p essu e eadings a e consis en ly 140/90mm Hg o abo e. Fo
each case, a leas 1 no mo ensi e con ol wi h he same sex and
simila smoking habi s we e chosen om a PHE coho (n=6000).
Smoking s a us was e alua ed based on sel - epo ing.
Using he pa ien ’s na ional iden i y code, da a on hospi al-
iza ions including ICD-10 codes o discha ge diagnoses we e
ob ained om he Finnish Na ional Hospi al Discha ge Regis y
(HILMO) main ained by he Na ional Ins i u e o Heal h and
Wel a e. P e alence o ischemic hea diseases (I20-I25) we e
ollowed up om 2005 o 2014 un il he subjec s we e on he
a e age 60 yea s old.
Buccal swabs o DNA ex ac ion and a pe missions o m o
use PHE da a we e collec ed by mail sepa a ely o he physical
examina ion. The DNA samples we e collec ed du ing yea s
2006–2010. In o med consen was ob ained om all pa ic-
ipan s. The E hics Commi ees o he Tampe e Uni e si y
Hospi al and he Ci y o Tampe e app o ed he s udy.
2.2. Geno yping
DNA was ex ac ed om buccal swabs using a comme cial
ki (Qiagen Inc., Valencia, CA). Geno yping was pe o med
using KASP (Compe i i e Allelic Specific Amplifica ion) geno yp-
ing se ices a KBioscience Ins i u e, UK. De ails o his me hod
can be ob ained om h ps://www.lgcg oup.com/geno yping/.
2.3. S a is ical analysis
S a is ical analyses we e pe o med using IBM SPSS S a is ics 23,
and Ha dy–Weinbe g equilib ium o he geno ypes was calcula ed
using OEGE (online encyclopedia calcula o o gene ic epidemi-
ology s udies).
[17]
T- es and 1-way ANOVA o con inuous
a iables (clinical cha ac e is ics) and chi-squa e es o ca ego i-
cal a iables (hype ension, co ona y a e y disease) we e applied
o he compa ison o HJV geno ype g oups. Associa ions o he
geno yped HJV gene a ian s wi h hype ension/co ona y a e y
disease wi h isk ac o s (BMI, glucose, choles e ol and gende )
we e analyzed using logis ic eg ession analysis. P- alues less han
0.05 we e conside ed significan .
3. Resul s
Clinical cha ac e is ics o he s udy popula ion a he age o 50
yea s a e p esen ed in Table 1. B iefly, he case g oup comp ised
336 hype ensi e cases and con ol g oup 480 no mo ensi e
subjec s wi h he same sex dis ibu ion and simila smoking
habi s. A o al o 78 subjec s we e ound o ha e co ona y a e y
disease when ollowed up o 60 yea s o age.
Geno yping was success ul in 808 subjec s o he HJV
s16827043 (A>G) and in 795 subjec s o he s7536827 (A>
T). The measu ed geno ype equencies we e no significan ly
di e en om he expec a ions o Ha dy–Weinbe g equilib ium
(x
2
=0.22 o s16827043 and x
2
=0.09 o s7536827). The
clinical cha ac e is ics acco ding o di e en geno ypes a e
shown in Tables 2 and 3.
Table 1
Clinical cha ac e is ics o cases and con ols o he s udy popula ion and subpopula ion wi h BMI <30.
S udy popula ion Subpopula ion wi h BMI<30
Cases (n=336) Con ols (n=480) P(Cases n=239) Con ols (n=399) P
Age, y 50±050±050±050±0
BMI, kg/m
2
28.8±5.1 25.5 ±3.7 <0.001 25.9±2.8 24.8±2.7 <0.001
Hemoglobin 147.0±13.4 145.4±13.2 0.165 146.3±13.0 144.8±13.1 0.240
Choles e ol, mmol/L 5.38±0.99 5.37 ±0.88 0.887 5.42±1.02 5.37 ±0.88 0.510
LDL choles e ol, mmol/L 3.16±0.88 3.17 ±0.82 0.838 3.15±0.92 3.16 ±0.83 0.921
Glucose, mmol/L 5.17±1.29 4.86 ±0.53 <0.001 5.11±1.45 4.85±0.53 0.001
Sys olic blood p essu e, mm Hg 142.7±16.6 129.3±14.8 <0.000 142.7±17.0 128.4±14.3 <0.000
Dias olic blood p essu e, mm Hg 92.8±8.8 84.4±9.1 <0.000 92.7±8.9 83.8±8.7 <0.000
Hype ension % 100 0 100 0
Diabe es % 12.8 0 <0.000 9.6 0 <0.000
Myoca dial in a c ion % 3.6 0 <0.000 3.2 0 0.001
Exe cise, a leas wice a week, % 62.8 57.2 0.135 62.8 55.5 0.102
Family his o y o hype ension % 71.6 42.5 <0.000 74.7 41.5 <0.000
Gende , male, % 58.4 56.8 0.319 58.3 64.1 0.165
Da a is p esen ed as mean ±SD
BMI =body mass index, LDL =low densi y lipop o ein, SD=s anda d de ia ion.
Nikka i e al. Medicine (2017) 96:5 Medicine
2
Fo HJV polymo phism s16827043, he e we e only 3
indi iduals who we e homozygous o he GG geno ype and hey
we e combined o he GA geno ype g oup. A he age o 50 yea s,
58 o 111 G-allele ca ie s (52,2%) had diagnosed hype ension
compa ed o 287 o 697 (41.3%) o hose homozygous o he
wild ype (AA), espec i ely (P=0.041). Also, dias olic blood
p essu e eadings we e significan ly highe among G-allele
ca ie s (Table 2). When he isk o hype ension was analyzed
by logis ic eg ession using HJV a ian s, BMI, glucose,
choles e ol, and gende as explainable a iables, OR o HJV
G-allele ca ie s was 1.66 (P=0.03, 95% CI: 1.06–2.60), o BMI
1.19 (P<0.001, 95% CI: 1.15–1.24), o glucose 1.49 (P<
0.001, 95% CI: 1.16–1.92), o choles e ol 0.99 (P=0.96, 95%
CI: 0.84–1.18), and o gende 1.50 (P=0.02, 95% CI:
1.07–2.09) compa ed wi h AA geno ype. In o de o exclude
he s ong e ec o BMI on hype ension, we also analyzed a
subpopula ion o he s udy pa icipan s wi h no mal o only
sligh ly ele a ed BMI. When o e weigh pa icipan s (BMI>30)
we e excluded om he analyses, he isk o hype ension among
G-allele ca ie s emained significan (OR=1.80, 95% CI
1.09–2.98, P=0.02). Adjus ed and unadjus ed esul s a e in
Table 4. No s a is ically significan associa ion wi h co ona y
a e y disease was ound (Table 2).
Fo he o he polymo phic si e ( s7536927, T>A), no
associa ion be ween geno ypes o combined alleles and hype -
ension was ound in he whole s udy popula ion (P=0.29 o
geno ypes and P=0.24 o A-allele ca ie s). Howe e ,
when subjec s we e s a ified acco ding o weigh , ca ie s o
he A-allele whose BMI was less han 30 had mo e o en
hype ension compa ed wi h hose homozygous o he wild ype
(TT) (OR=1.56, P=0.04, 95% CI 1.01–2.39) (Table 4.) As wi h
he s7536827, no associa ion wi h co ona y a e y disease was
ound (Table 2).
4. Discussion
The esul s o he p esen s udy sugges ha gene ic a ia ion in
he HJV gene is significan ly associa ed wi h hype ension in a 50-
yea -old Finnish popula ion. P e ious s udies o he HJV and
HFE gene ic polymo phisms ha e concen a ed mainly on
hemoch oma osis. Ou esul s and hose o o he s indica e ha
dis u bances in i on me abolism may also inc ease he isk o
hype ension.
[18,19]
We ound no impac o he 2 s udied HJV
polymo phisms on co ona y a e y disease.
In his pape , we show ha he mino allele G o he
HJV a ian s16827043 was associa ed wi h hype ension.
In addi ion, he associa ion be ween he mino allele and
hype ension was e en s onge among no mal- o only
sligh ly o e weigh subjec s. Fo he o he HJV polymo phic
si e s7536827, no s a is ically significan associa ion
wi h hype ension was ound. Howe e , when T allele ca ie s
we e combined and obese subjec s we e excluded, also his
gene ic a ia ion associa ed wi h hype ension. Al hough he
mechanism is no known, ou esul oge he wi h p e ious ones
p o ides a u he link be ween i on me abolism and
hype ension.
[11–13,20]
Mild i on o e load is one possible explana ion o highe
blood p essu e o ca ie s o he HJV mino a ian s, as has been
sugges ed o H63D.
[13]
Bo h o hese memb ane ecep o s a e
in ol ed in pa hways leading o hepcidin ansc ip ion. A ecen
Table 2
Clinical cha ac e is ics o he s udy popula ion s a ified acco ding o HJV s 16827043 geno ypes.
HJV PP
s16827043 AA AG GG AA s AG s GG AA s (AG+ GG)
n a 50 697 108 3
Hype ension % 41.3 51.0 100 0.024 0.041
Co ona y a e y disease, %, n=78 9.9 8.3 0 0.745 0.729
Sys olic blood p essu e, mm Hg 134. 7±16.8 137.7 ±16.7 136.7±13.3 0.237 0.095
Dias olic blood p essu e, mm Hg 87.7±9.8 89.6±9.7 98.9±7.2 0.035 0.033
Body mass index, kg/m
2
26.9±4.7 27.1 ±4.2 25.5±2.3 0.784 0.746
Choles e ol, mmol/L 5.35±0.99 5.55 ±0.90 5.53±0.97 0.151 0.052
Glucose, mmol/L 5.03±1.20 5.02 ±0.68 4.83±0.25 0.953 0.898
HJV =hemoju elin (p e iously HFE2).
P alues om he chi-squa e es o ca ego ical a iables and 1 way ANOVA o T- es o con inuous a iables.
P alues <0.05 a e in bold.
Table 3
Clinical cha ac e is ics o he s udy popula ion s a ified acco ding o HJV s 7536827 geno ypes.
HJV PPP
s7536827 AA AT TT AA s AT s TT AA s (AT+TT) TT s (AA+AT)
n a 50 186 397 212
Hype ension % 39.2 45.5 40.9 0.293 0.602 0.241
Co ona y a e y disease, %, n=78 8.1 10.4 9.4 0.680 0.161 1.000
Sys olic blood p essu e, mm Hg 134.9±16.3 135.5±16.6 134.4±17.7 0.738 0.898 0.475
Dias olic blood p essu e, mm Hg 87.6±10.2 88.5±9.7 87.4±9.6 0.362 0.529 0.302
BMI, kg/m
2
26.6±4.8 27.1±4.6 26.9±4.5 0.406 0.250 0.767
Choles e ol, mmol/L 5.37±0.95 5.34±1.05 5.46±0.89 0.340 0.846 0.151
Glucose, mmol/L 5.03±0.91 5.01±1.19 5.07±1.24 0.841 0.949 0.567
BMI =body mass index.
P alues om he chi-squa e es o ca ego ical a iables and 1-way ANOVA o T- es o con inuous a iables.
P alues <0.05 a e in bold.
Nikka i e al. Medicine (2017) 96:5 www.md-jou nal.com
3
s udy has epo ed ha HJV unc ions as enhance o i on
signaling o hepcidin. Since hepcidin is he main i on egula o y
ho mone, dis u bances in pa hways a ec ing hepcidin exp ession
may block i s unc ion as a eedback inhibi o o i on abso p ion.
Howe e , only comple e loss o hepcidin in humans is esponsible
o a e ye se e e o ms o massi e body i on o e load.
[21]
In Finland, es s o assessing body i on le els (se um e i in
and ans e in sa u a ion) a e no ou inely measu ed and
he e o e a limi a ion o he TAMRISK s udy popula ion is he
lack o hese sa u a ion ma ke s. Howe e , i has p e iously been
published ha men wi h essen ial hype ension had g ea e i on
s o es han no mo ensi e con ols.
[20]
I is known ha p e alence o hype ension is highe in obese
han in lean popula ions and he e is nea ly linea ela ionship
be ween BMI and blood p essu e.
[22]
I has p e iously been shown
ha he e is a gene-en i onmen al associa ion be ween hype en-
sion genes and BMI. Thus, obesi y will o e ide he gene ic
e ec .
[13,23]
The associa ion o HJV and hype ension was simila
o e en s onge o no mal weigh and sligh ly o e weigh subjec s
han in obese subjec s, confi ming he ole o HJV.
Al hough he mechanism is no ye known, ou esul s sugges
ha he mino allele G o he HJV a ian ( s16827043) is
associa ed wi h highe isk o hype ension a he age o 50
yea s, compa ed wi h he AA-geno ype ca ie s. In addi ion, we
ound ha among no mal o sligh ly o e weigh indi iduals, also
T-allele o he HJV s7536827 inc eases he isk o hype ension.
I is he e o e possible ha dys egula ion in i on me abolism is a
significan ac o behind hype ension. Abno mali ies in i on
homeos asis and ela ionship be ween i on me abolism and
hype ension wa an u he s udies.
Acknowledgmen s
The au ho s hank all o he pa icipan s o he TAMRISK s udy
and Mi ka Pie iläinen and Ulla Saa ijoki o hei skil ul echnical
assis ance.
Re e ences
[1] C owno e B, Co ey C. He edi a y hemoch oma osis. Am Fam
Physician 2013;87:183–90.
[2] Means RTJ . Hepcidin and i on egula ion in heal h and disease. Am J
Med Sci 2013;345:57–60.
[3] Lo eal O, Haziza-Pigeon C, T oadec M, e al. Hepcidin in i on
me abolism. Cu P o ein Pep ide Sci 2005;6:279–91.
[4] Nicolas G, Chau e C, Via e L, e al. The gene encoding he i on
egula o y pep ide hepcidin is egula ed by anemia, hypoxia and
inflamma ion. J Clin In es 2002;110:1037–44.
[5] Sil a B, Faus ino P. An o e iew o molecula basis o i on me abolism
egula ion and he associa ed pa hologies. Biochimica e Biophysica Ac a
2015;1852:1347–59.
[6] Babi JL, Huang FW, W igh ing DM, e al. Bone mo phpgene ic p o ein
signaling by hemoju elin egula es hepcidin exp ession. Na Gene
2006;38:531–9.
[7] Ken P, Wilkinson N, Cons an e M, e al. H e and Hj exhibi
o e lapping unc ions o i on signaling o hepcidin. J Mol Med
2015;93:489–98.
[8] Wu Q, Wang H, An P, e al. HJV and HFE play dis inc oles in
egula ing hepcidin. An ioxid Redox Signal 2015;22:1325–36.
[9] Fede J, Gni ke A, Thomas W, e al. A no el MCH class I-like gene is
mu a ed in pa ien s wi h he edi a y haemoch oma osis. Na u e Gene
1996;13:399–408.
[10] Papanikolaou G, Samuels ME, Ludwig EH, e al. Mu a ions in HFE2
cause i on o e load in ch omosome 1q-linked ju enile hemoch oma o-
sis. Na Gene 2004;36:77–82.
[11] Eh e GB, Mun oe PB, Rice KM, e al. Gene ic a ian s in no el
pa hways influence blood p essu e and ca dio ascula disease isk.
Na u e 2011;478:103–9.
[12] Lu X, Wang L, Lin X, e al. Genome-wide associa ion s udy in Chinese
iden ifies no el logi o blood p essu e and hype ension. Hum Mol
Gene 2015;24:865–74.
[13] Mää ä KM, Nikka i ST, Kunnas TA. Gene ic a ian coding o i on
egula o y p o ein HFE con ibu es o hype ension, he TAMRISK
s udy. Medicine (Bal imo e) 2015;94:e464.
[14] Co e A, Canali S, Babi J. Hemoju elin and bone mo phogene ic
p o ein (BMP) signaling in i on homeos asis. F on Pha macol 2014;5:
104.
[15] Mile J, Dehais V, Bou gain C, e al. Common a ian s in he BMP2,
BMP4 and HJV genes o he hepcidin egula ion pa hway modula e HFE
hemoch oma osis pene ance. Am J Hum Gene 2007;81:799–807.
[16] Mää ä KM, Nikka i ST, Läh eelä KH, e al. A unc ional a ian in he
se ine- h eonine kinase coding gene is associa ed wi h hype ension: a
case-con ol s udy in a Finnish popula ion, he Tampe e adul popula ion
ca dio ascula isk s udy. J Hype ension 2013;31:516–20.
[17] Rod igues S, Gaun TR, Day INM. Ha dy–Weinbe g equilib ium es ing
o biological asce ainmen o Mendelian andomiza ion s udies. Am J
Epidemiol 2009;169:505–14.
[18] Na eka A, Olds RL, Lau MW, e al. Ele a ed blood p essu e: ou
amily’s aul ? The gene ics o essen ial hype ension. Wo d J Ca diol
2014;6:327–37.
[19] Valen i L, Malobe i A, Signo ini S, e al. I on s o es, hepcidin, and ao ic
s i ness in indi iduals wi h hype ension. Plos One 2015;10:e0134635.
[20] Pipe no A, T ombini P, Gelosa M, e al. Inc eased se um e i in is
common in men wi h essen ial hype ension. J Hype ens 2002;20:
1513–8.
[21] Pie angelo A. Gene ics, gene ic es ing, and managemen o hemoch o-
ma osis: 15 yea s since hepcidin. Gas oen e ology 2015;149:1240–51.
[22] Weinbe ge MH, Finebe g NS, Finebe g SE, e al. Sal sensi i i y, pulse
p essu e, and dea h in no mal and hype ensi e humans. Hype ension
2001;37:429–32.
[23] Ma eau J-B, Sass C, Pfis e M, e al. The Leu554Phe polymo phism in
he E-selec in gene is associa ed wi h blood p essu e in o e weigh
people. J Hype ens 2004;22:305–11.
Table 4
Unadjus ed and adjus ed OR esul s ob ained om logis ic eg ession analysis o hype ension.
Uni a ia e model
∗
Mul i a ia e model
†
OR (95% CI) POR (95% CI) P
All pa icipan s
s16827043, G-allele s AA 1.54 (1.02–2.32) 0.041 1.66 (1.06–2.60) 0.028
s7536827, A-allele s TT 1.26 (0.88–1.69) 0.247 1.36 (0.94–1.98) 0.103
BMI<30 kg/m
2
OR (95% CI) POR (95% CI) P
s16827043, G-allele s AA 1.70 (1.05–2.75) 0.032 1.80 (1.09–2.98) 0.022
s7536827, A-allele s TT 1.48 (0.99–2.22) 0.056 1.56 (1.01–2.39) 0.044
BMI=body mass index, CI=confidence in e al, OR =odds a io.
∗
Uni a ia e model wi h HJV SNP alone
†
Mul i a ia e
2
model wi h HJV SNP, BMI, glucose, choles e ol, and gende as explainable a iables
4
Nikka i e al. Medicine (2017) 96:5 Medicine