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ß2-adrenergic receptor Thr164Ile polymorphism, obesity, and diabetes: comparison with FTO, MC4R, and TMEM18 polymorphisms in more than 64,000 individuals.

https://arctichealth.org/en/permalink/ahliterature125626
Source
J Clin Endocrinol Metab. 2012 Jun;97(6):E1074-9
Publication Type
Article
Date
Jun-2012
Author
Mette Thomsen
Morten Dahl
Anne Tybjærg-Hansen
Børge G Nordestgaard
Author Affiliation
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark.
Source
J Clin Endocrinol Metab. 2012 Jun;97(6):E1074-9
Date
Jun-2012
Language
English
Publication Type
Article
Keywords
Adult
Body mass index
Cohort Studies
Denmark - epidemiology
Diabetes Mellitus - epidemiology - genetics
Female
Genetic Predisposition to Disease - epidemiology - genetics
Genotype
Humans
Male
Membrane Proteins - genetics
Obesity - epidemiology - genetics
Polymorphism, Single Nucleotide - genetics
Proteins - genetics
Receptor, Melanocortin, Type 4 - genetics
Receptors, Adrenergic, beta-2 - genetics
Risk factors
Abstract
The ß(2)-adrenergic receptor (ADRB2) influences regulation of energy balance by stimulating catecholamine-induced lipolysis in adipose tissue. The rare functional ADRB2rs1800888(Thr164Ile) polymorphism could therefore influence risk of obesity and subsequently diabetes.
We tested the hypothesis that the ADRB2rs1800888(Thr164Ile) polymorphism associates with risk of obesity and diabetes and compared effect sizes with those of FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238).
We conducted a population-based cohort study in Copenhagen, Denmark.
We genotyped more than 64,000 individuals from the Danish general population.
We evaluated body mass index (BMI), obesity (BMI =30 kg/m(2)), and diabetes.
Rare allele frequencies were 0.02 for T for ADRB2rs1800888(Thr164Ile), 0.40 for A for FTOrs9939609, 0.25 for C for MC4Rrs17782313, and 0.20 for T for TMEM18rs6548238. For rare vs. common homozygotes, odds ratio for obesity was 3.32 (95% confidence interval = 1.08-10.19) for ADRB2rs1800888(Thr164Ile), 1.42 (1.35-1.52) for FTOrs9939609, 1.18 (1.06-1.30) for MC4Rrs17782313, and 1.28 (1.10-1.50) for TMEM18rs6548238 (common vs. rare). Corresponding odds ratios for diabetes were 1.85 (0.24-14.29), 1.22 (1.07-1.39), 0.96 (0.80-1.16), and 1.61 (1.17-2.22), respectively. After adjustment for BMI, only TMEM18rs6548238 remained associated with diabetes. BMI was increased in rare vs. common homozygotes in FTOrs9939609, MC4Rrs17782313, and TMEM18rs6548238 (common vs. rare) but not in ADRB2rs1800888(Thr164Ile).
Our results suggest that ADRB2rs1800888(Thr164Ile) rare vs. common homozygotes are not significantly associated with an increase in BMI measured continuously but may be associated with an increased risk of obesity. Also, TMEM18rs6548238 associated with risk of diabetes after adjustment for BMI. These findings need confirmation in other studies.
PubMed ID
22466342 View in PubMed
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[A comparative analysis of tuberculosis susceptibility genetic make-up in Tuvinians and Russians]

https://arctichealth.org/en/permalink/ahliterature82359
Source
Mol Biol (Mosk). 2006 Mar-Apr;40(2):252-62
Publication Type
Article
Author
Freidin M B
Rudko A A
Kolokolova O V
Ondar E A
Strelis A K
Puzyrev V P
Source
Mol Biol (Mosk). 2006 Mar-Apr;40(2):252-62
Language
Russian
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Alleles
Ethnic Groups
Female
Gene Frequency - genetics
Genetic Predisposition to Disease - epidemiology - genetics
Haplotypes
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Siberia - epidemiology - ethnology
Tuberculosis - epidemiology - ethnology - genetics
Abstract
The results of the first Russian study of polymorphisms of tuberculosis (TB) susceptibility genes SLC11A1, VDR, IL12B, IL1B, IL1RN in Tuvinians from Tuva Republic and Russians from Tomsk city are presented. In Tuvinians, as compared with Russians, the significantly higher prevalence of potentially disease-associated alleles of the genes studied was shown: SLC11A1*543N (0.139 and 0.043, respectively, p = 4.6E-5), IL12B*1188C (0.378 and 0.174, respectively, p = 1.1E-8), VDR*b (0.825 and 0.532, respectively, p = 3.2E-16), IL1B*(+3953A1) (0.865 and 0.806, respectively, p = 0.035). However, no one of these alleles was associated with TB in Tuvinians, whereas, in Russians TB patients, in comparison with the controls, there was a higher prevalence of the following markers: IL1RN*A2 (0.258 and 0.186, respectively, p = 0.024), SLC11A1*274T (0.251 and 0.164, respectively, p = 0.009), IL12B*1188C (0.240 and 0.174, respectively, p = 0.044), ILIB*(+3953A2) (0.259 and 0.194, respectively, p = 0.044). Distinct patterns of linkage disequilibrium between pairs of the polymorphisms studied in Tuvinians and Russians were shown. At whole, the data obtained demonstrate the ethnic specificity of the distribution and pathogenetic significance of the alleles of the TB susceptibility genes.
PubMed ID
16637265 View in PubMed
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[Analysis of genetic predisposition to pulmonary tuberculosis in native Russians].

https://arctichealth.org/en/permalink/ahliterature144799
Source
Genetika. 2010 Feb;46(2):262-71
Publication Type
Article
Date
Feb-2010
Author
O A Gra
Zh M Kozhekbaeva
V I Litvinov
Source
Genetika. 2010 Feb;46(2):262-71
Date
Feb-2010
Language
Russian
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Alleles
Cation Transport Proteins - genetics
Cohort Studies
Cytochrome P-450 Enzyme System - genetics
Female
Gene Frequency - genetics
Genetic Predisposition to Disease - epidemiology - genetics
Genotype
Glutathione Transferase - genetics
Humans
Male
Middle Aged
Moscow - epidemiology - ethnology
P-Glycoprotein - genetics
Tuberculosis, Pulmonary - epidemiology - genetics
Abstract
Tuberculosis (TB) is one of the most important concerns of public health. There is evidence suggesting that genetic status is responsible for predisposition to infectious diseases including TB. To determine genetic risk factors of TB development, the frequencies of polymorphisms of genes CYP1A1, CYP2D6, CYP2C9, CYP2C 19, GSTT1, GSTM1, NAT2, MDR1, and NRAMP1 in 73 TB patients and 352 healthy individuals were determined by allele-specific hybridization using microarray technology. The TB patients have shown a significant increase in the frequency of the null GSTT1 genotype (OR = 3.26, 95% CI = 1.91 - 5.55, p = = 0.000028) as well as the double null GSTT1/GSTM1 genotype (OR = 4.05, 95% CI = 2.14 -7.65, p = = 0.000034) compared to the group of healthy donors. It was shown that the NAT2*5/*5 genotype in combination with the "null" GSTT1 and the double "null" GSTT1/GSTM1 genotypes was observed significantly more often in the TB patients than in the control sample. Thus the examined GSTT1, GSTM1 and NAT2 gene polymorphisms may potentially alter the risk of TB development in ethnic Russians and are of interest for further research using larger cohorts of patients.
PubMed ID
20297661 View in PubMed
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Analysis of the SORT1 gene in familial amyotrophic lateral sclerosis.

https://arctichealth.org/en/permalink/ahliterature126744
Source
Neurobiol Aging. 2012 Aug;33(8):1845.e7-9
Publication Type
Article
Date
Aug-2012
Author
Véronique V Belzil
Catherine André-Guimont
Marie-Renée Atallah
Hussein Daoud
Nicolas Dupré
Jean-Pierre Bouchard
William Camu
Patrick A Dion
Guy A Rouleau
Author Affiliation
Centre of Excellence in Neurosciences of Université de Montréal, CHUM Research Center, Montreal, QC H2L 4M1, Canada.
Source
Neurobiol Aging. 2012 Aug;33(8):1845.e7-9
Date
Aug-2012
Language
English
Publication Type
Article
Keywords
Adaptor Proteins, Vesicular Transport - genetics
Adolescent
Adult
Amyotrophic Lateral Sclerosis - congenital - epidemiology - genetics
Child
Female
Genetic Markers - genetics
Genetic Predisposition to Disease - epidemiology - genetics
Humans
Male
Mutation - genetics
Polymorphism, Single Nucleotide - genetics
Prevalence
Quebec - epidemiology
Risk factors
Young Adult
Abstract
Substantial efforts have been deployed in the past decade to identify the genetic causes of amyotrophic lateral sclerosis (ALS), and we hypothesized here that mutations in SORT1 or aberrant SORT1 splicing reduce progranulin level and promote neurodegeneration.
We sequenced the coding exons of SORT1 in a cohort of 112 unrelated individuals with familial ALS. We also tested for aberrant SORT1 splicing by RT-PCR using RNA samples from cell lines expressing six different ALS-associated TARDBP mutations.
We identified one unique missense and two unique silent mutations in our cohort. None are predicted to have functional effects. No aberrant SORT1 splicing event was observed.
SORT1 mutations are not a common cause of familial ALS, and the influence of TARDBP mutations on SORT1 splicing still needs to be clarified.
PubMed ID
22361451 View in PubMed
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Apolipoprotein E epsilon4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging.

https://arctichealth.org/en/permalink/ahliterature178000
Source
CMAJ. 2004 Oct 12;171(8):863-7
Publication Type
Article
Date
Oct-12-2004
Author
Ging-Yuek R Hsiung
A Dessa Sadovnick
Howard Feldman
Author Affiliation
Department of Medicine, Clinic for Alzheimer's Disease and Related Disorders, University of British Columbia, Vancouver, BC.
Source
CMAJ. 2004 Oct 12;171(8):863-7
Date
Oct-12-2004
Language
English
Publication Type
Article
Keywords
Aged
Alzheimer Disease - epidemiology - genetics
Apolipoprotein E4
Apolipoproteins E - genetics
Canada - epidemiology
Case-Control Studies
Cognition Disorders - epidemiology - genetics
Dementia, Vascular - epidemiology - genetics
Disease Progression
Female
Genetic markers
Genetic Predisposition to Disease - epidemiology - genetics
Humans
Incidence
Logistic Models
Longitudinal Studies
Male
Multivariate Analysis
Predictive value of tests
Risk factors
Abstract
Apolipoprotein E (ApoE) epsilon4 genotype is a well-established risk factor for Alzheimer's disease (AD). However, its effect on predicting conversion from normal to "cognitive impairment, no dementia" (CIND) and from CIND to AD is less clear.
We used a nested case-control design from the population-based Canadian Study of Health and Aging (CSHA) to examine the effect of ApoE epsilon4 genotype on the conversion of subjects from normal to CIND and from CIND to AD. We also contrasted these findings with incident cases of AD and vascular dementia (VaD) in the CSHA cohort.
The ApoE epsilon4 genotype was a significant risk factor for conversion from CIND to AD and from normal to AD and VaD. However, it was not a significant risk factor for conversion from normal to CIND. This effect is robust to adjustment for age, sex and education level. There is significant interaction between the ApoE epsilon4 genotype and age for AD and for conversion from CIND to AD. No interaction between ApoE epsilon4 genotype, sex, age, ethnicity and education level was found in other subgroup analyses. The positive predictive value of ApoE epsilon4 for predicting CIND conversion to AD was 0.48, and the negative predictive value was 0.65.
Possession of an ApoE epsilon4 allele increases the risk of AD developing from CIND. It is also associated with a decrease in the age at onset of AD. Its predictive values do not support its utility as a diagnostic test for predicting progression from CIND to AD, but it may be useful in research studies to enrich study samples that have a higher rate of progression to AD.
Notes
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Comment In: CMAJ. 2004 Oct 12;171(8):88115477627
PubMed ID
15477624 View in PubMed
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Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway: results from a family-based screening program.

https://arctichealth.org/en/permalink/ahliterature179624
Source
Semin Vasc Med. 2004 Feb;4(1):75-85
Publication Type
Article
Date
Feb-2004
Author
Trond P Leren
Turid Manshaus
Unn Skovholt
Tove Skodje
Inger Esther Nossen
Christél Teie
Stine Sørensen
Kari Solberg Bakken
Author Affiliation
Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet, Oslo, Norway. trond.leren@rikshospitalet.no
Source
Semin Vasc Med. 2004 Feb;4(1):75-85
Date
Feb-2004
Language
English
Publication Type
Article
Keywords
Biological Markers - blood
Disease Management
Family Health
Genetic Predisposition to Disease - epidemiology - genetics
Genetic Testing
Humans
Hyperlipoproteinemia Type II - diagnosis - therapy
Lipids - blood
Molecular Biology
Norway - epidemiology
Abstract
A total of 119 different mutations in the low-density lipoprotein-receptor gene have so far been found to cause familial hypercholesterolemia (FH) among Norwegian patients. As of April 2003, 2390 patients from 959 unrelated families were provided with a molecular genetic diagnosis. Of these, 25.3% had xanthomas and 8.4% had xanthelasma. During the last 2-3 years, a systematic family-based program to identify close relatives of FH patients has been established. A total of 851 relatives of 188 index patients have undergone genetic testing. Four hundred seven people (47.9%) were affected, and 444 (52.1%) were unaffected. Only 41.5% of those affected were on lipid-lowering drugs, and only 6.1% had a value for total serum cholesterol below 193 mg/dL (5.0 mmol/L). A follow-up study was conducted in 146 of 407 affected relatives 6 months after genetic testing was performed. Of those already under treatment at the time of genetic testing, nonsignificant reductions of total serum cholesterol and low-density lipoprotein cholesterol of 3.2% and 7.1% were observed. Of those not under treatment who were aged 18 years and older, the corresponding reductions were 21.2% (p
PubMed ID
15199436 View in PubMed
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Association between genetic variants in the tumour necrosis factor/lymphotoxin a/lymphotoxin ß locus and primary Sjogren's syndrome in Scandinavian samples.

https://arctichealth.org/en/permalink/ahliterature127439
Source
Ann Rheum Dis. 2012 Jun;71(6):981-8
Publication Type
Article
Date
Jun-2012
Author
Anne Isine Bolstad
Stephanie Le Hellard
Gudlaug Kristjansdottir
Lilian Vasaitis
Marika Kvarnström
Christopher Sjöwall
Svein Joar Auglænd Johnsen
Per Eriksson
Roald Omdal
Johan G Brun
Marie Wahren-Herlenius
Elke Theander
Ann-Christine Syvänen
Lars Rönnblom
Gunnel Nordmark
Roland Jonsson
Author Affiliation
Department of Clinical Dentistry--Periodontics, University of Bergen, Bergen, Norway. anne.bolstad@iko.uib.no
Source
Ann Rheum Dis. 2012 Jun;71(6):981-8
Date
Jun-2012
Language
English
Publication Type
Article
Keywords
Adult
Aged
Cohort Studies
European Continental Ancestry Group - genetics - statistics & numerical data
Female
Genetic Predisposition to Disease - epidemiology - genetics
Genetic Variation
Haplotypes
Humans
Linkage Disequilibrium
Lymphotoxin-alpha - genetics - immunology
Lymphotoxin-beta - genetics - immunology
Male
Middle Aged
Norway - epidemiology
Polymorphism, Single Nucleotide
Risk factors
Salivary Glands - immunology
Sjogren's Syndrome - epidemiology - genetics - immunology
Sweden - epidemiology
Tumor Necrosis Factor-alpha - genetics - immunology
Abstract
Lymphotoxin ? (LTB) has been found to be upregulated in salivary glands of patients with primary Sj?gren's syndrome (pSS). An animal model of pSS also showed ablation of the lymphoid organisation and a marked improvement in salivary gland function on blocking the LTB receptor pathway. This study aimed to investigate whether single-nucleotide polymorphisms (SNP) in the lymphotoxin a (LTA)/LTB/tumour necrosis factor (TNF) gene clusters are associated with pSS.
527 pSS patients and 532 controls participated in the study, all of Caucasian origin from Sweden and Norway. 14 SNP markers were genotyped and after quality control filtering, 12 SNP were analysed for their association with pSS using single marker and haplotype tests, and corrected by permutation testing.
Nine markers showed significant association with pSS at the p=0.05 level. Markers rs1800629 and rs909253 showed the strongest genotype association (p=1.64E-11 and p=4.42E-08, respectively, after correcting for sex and country of origin). When the analysis was conditioned for the effect of rs1800629, only the association with rs909253 remained nominally significant (p=0.027). In haplotype analyses the strongest effect was observed for the haplotype rs909253G_rs1800629A (p=9.14E-17). The associations were mainly due to anti-Ro/SSA and anti-La/SSB antibody-positive pSS.
A strong association was found between several SNP in the LTA/LTB/TNFa locus and pSS, some of which led to amino acid changes. These data suggest a role for this locus in the development of pSS. Further studies are needed to examine if the genetic effect described here is independent of the known genetic association between HLA and pSS.
PubMed ID
22294627 View in PubMed
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Association of cytochrome P450 1B1 polymorphism with first-trimester miscarriage.

https://arctichealth.org/en/permalink/ahliterature80646
Source
Fertil Steril. 2006 Nov;86(5):1498-503
Publication Type
Article
Date
Nov-2006
Author
Karypidis Anna-Helena
Söderström Torbjörn
Nordmark Anna
Granath Fredrik
Cnattingius Sven
Rane Anders
Author Affiliation
Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital (Huddinge), Stockholm, Sweden. helena.karypidis@ki.se
Source
Fertil Steril. 2006 Nov;86(5):1498-503
Date
Nov-2006
Language
English
Publication Type
Article
Keywords
Abortion, Spontaneous - epidemiology - genetics
Cytochrome P-450 Enzyme System - genetics
Female
Genetic Markers - genetics
Genetic Predisposition to Disease - epidemiology - genetics
Genetic Screening - methods
Humans
Polymorphism, Single Nucleotide - genetics
Pregnancy
Pregnancy Trimester, First - genetics
Prevalence
Risk Assessment - methods
Risk factors
Sweden - epidemiology
Abstract
OBJECTIVE: To determine whether the cytochrome P450 1B1 (CYP1B1) Val432Leu polymorphism is associated with risk of miscarriage. We also analyzed the possible interaction between this polymorphism and caffeine intake. DESIGN: The population-based case-control study included 507 women with miscarriage in the first trimester of pregnancy and 908 controls with a normal first-trimester pregnancy. The controls were frequency matched to cases. The material was analyzed taking maternal age, smoking habits, alcohol intake, caffeine intake, fetal karyotype, nausea, and vomiting into consideration. SETTING: University hospital and primary care facility. MAIN OUTCOME MEASURE(S): CYP1B1 Val432Leu genotype frequencies in cases and controls. RESULT(S): Carriers of the CYP1B1 432 Val/Val genotype were at a higher risk of miscarriage in the first trimester of pregnancy (odds ratio = 1.46; 95% confidence interval, 1.02-2.08). We also found a significant interaction between genotype and caffeine intake. CONCLUSION(S): CYP1B1 Val432Leu polymorphism is associated with first-trimester miscarriage, and it may also modify the risk among coffee drinkers.
PubMed ID
16978616 View in PubMed
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Association of HLA-DRB1*01 with Dupuytren's disease.

https://arctichealth.org/en/permalink/ahliterature120555
Source
Scand J Rheumatol. 2013;42(1):45-7
Publication Type
Article
Date
2013
Author
T. Jónsson
K G Gudmundsson
K. Bjarnadóttir
I B Hjálmarsdótti
S. Gudmundsson
R. Arngrímsson
Author Affiliation
The Blood Bank, Landspitali University Hospital, Reykjavík, Iceland.
Source
Scand J Rheumatol. 2013;42(1):45-7
Date
2013
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Cohort Studies
Dupuytren Contracture - epidemiology - genetics
European Continental Ancestry Group - genetics
Female
Gene Frequency
Genetic Predisposition to Disease - epidemiology - genetics
Genotype
HLA-DRB1 Chains - genetics
Health Surveys
Humans
Iceland - epidemiology
Male
Sex Distribution
Abstract
To explore the human leucocyte antigen (HLA)-DRB1 allele frequency in Dupuytren's disease (DD).
HLA-DRB1 genotypes were analysed by sequence-specific primers (SSPs) in samples collected from 172 men participating in a nested case-control study on the clinical manifestations and progression of DD. Of those, 121 had signs of DD while 51 did not. Of the 121 men with DD, 49 had contracted fingers or had been operated on, while 72 had nodules or fibrous cords in the palms. Odds ratios (ORs) and 95% confidence interval (CIs) were used to evaluate the results.
The HLA-DRB1*01 allele was observed in 26 of the 121 affected men (23.7%) but in only four of the controls (7.8%) (OR 3.22, 95% CI 1.06-9.75). The HLA-DRB1*01 allele frequency in those affected was 11%, while in the control group it was 4% (OR 3.07, 95% CI 1.05-9.03).
This observation indicates a possible association of HLA-DRB1*01 with DD, but further studies are needed for confirmation.
PubMed ID
22991974 View in PubMed
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Association of interleukin 8 with myocardial infarction: results from the Stockholm Heart Epidemiology Program.

https://arctichealth.org/en/permalink/ahliterature258580
Source
Int J Cardiol. 2014 Mar 1;172(1):173-8
Publication Type
Article
Date
Mar-1-2014
Author
Ilais Moreno Velásquez
Paolo Frumento
Katarina Johansson
Anita Berglund
Ulf de Faire
Karin Leander
Bruna Gigante
Source
Int J Cardiol. 2014 Mar 1;172(1):173-8
Date
Mar-1-2014
Language
English
Publication Type
Article
Keywords
Aged
Case-Control Studies
Coronary Artery Disease - epidemiology - genetics - metabolism
Female
Genetic Predisposition to Disease - epidemiology - genetics
HapMap Project
Humans
Interleukin-8 - blood - genetics
Logistic Models
Male
Middle Aged
Myocardial Infarction - epidemiology - genetics - metabolism
Odds Ratio
Polymorphism, Single Nucleotide
Receptors, Interleukin-8A - genetics - metabolism
Receptors, Interleukin-8B - genetics - metabolism
Risk factors
Sweden - epidemiology
Abstract
Interleukin 8 (IL8) has been contradictorily associated with the risk of myocardial infarction (MI).
To investigate the association of IL8 serum levels with the risk of MI and the association of the IL8 (IL8) and IL8 receptors (CXCR1 and CXCR2) genetic variants with IL8 levels and MI risk in a large case control study, the Stockholm Heart Epidemiology Program.
IL8 levels (pg/mL) were divided into quartiles and the MI risk was calculated by logistic regression and expressed as odds ratio (OR) and 95% CI. Two IL8 SNPs (rs4073A/T, rs2227306C/T) and three SNPs tagging CXCR1 and CXCR2 (rs4674258C/T, rs1008563C/T, rs6723449T/C) were analyzed for association with IL8 levels and with MI risk. Multivariate adjusted ORs for MI risk by IL8 levels in the highest quartiles indicated reduced point estimates in both women (OR 0.37; 95% CI 0.2-0.8) and men when compared to the lowest quartile. In female cases, IL8 levels decreased progressively in the six months after MI (p=0.03). IL8, CXCR1 and CXCR2 genetic variants were not associated with IL8 levels. In men, the T allele at the IL8 SNP rs4073 was associated with a slight increase in the MI risk under an additive and a recessive model of inheritance.
IL8 serum levels were associated with a reduced occurrence of MI among women, whereas IL8 was associated with a slightly increased risk among men, possibly through different mechanisms. These data suggest that the biological effects of IL8 on MI risk may vary over time and warrant further cohort studies with repetitive IL8 measurements.
PubMed ID
24462138 View in PubMed
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129 records – page 1 of 13.