exercise rehabilitation provides benefit to assisting in the physical state including blood pressure , blood sugar , and vessel elasticity in obesity ( lee et al . , 2013 ) . although exercise rehabilitation is effective in obesity patients , there are various differences among obesity patients . hence , it is important to find clinical characters of obesity patients in order to do exercise rehabilitation . obesity is the primary metabolic disorder and is well known to play a key role in the development of a number of metabolic abnormalities ( pi - sunyer , 2002 ) . obesity increases the susceptibility of many diseases , such as type 2 diabetes mellitus , hypertension , and various cancers ( foss and dyrstad , 2011 ) . obesity is characterized by an increased adipose tissue mass with large size and mature adipocytes . environmental , behavioral , and genetic factors have been known to contribute to the etiology of obesity ( foss and dyrstad , 2011 ) . previous studies investigated that the il1 system was contributed to metabolism ( erion et al . il1rn has an anti - inflammatory function by blocking the receptor for il1a and il1b without exerting any biological effect ( juge - aubry and meier , 2002 ) . il1rn showed high level in the serum of obese patients and overexpressed in white adipose tissue . it indicated that il1rn is an important regulator of adipogenesis , food intake , and energy expenditure in obesity . in this study , we investigated whether polymorphisms of the il-1rn gene are associated with the development of obesity . subjects were recruited among participants who examined a general health check - up program . each subject was calculated body mass index ( bmi ) , systolic blood pressure ( sbp ) , and diastolic blood pressure ( dbp ) . bmi was also used by dividing the subject s mass by the square of height ( kg / m ) . according to the classification of korean society for the study of obesity ( underweight , bmi<18 ; normal , bmi 18 to<23 ; moderately obese , bmi 23 to<25 ; obesity i , bmi 25 to<30 ; obesity ii , bmi30 ) , subjects were divided into two subgroups , the overweigh / obese group ( bmi23 , n=122 ) and the normal group ( 18<bmi<23 , n=123 ) . and overweigh / obese subjects also divided into two subgroups , the overweigh / obese with hypertension group ( > 130 mmhg in sbp/>85 mmhg in dbp , n=40 ) and the overweigh / obese with non - hypertension group ( < 130 mmhg in sbp/<85 mmhg in dbp , n=98 ) . the subjects with severe diseases , such as stroke , diabetic mellitus , and cancers were excluded in this study . ethical approval of this study was obtained from the ethics review committee of medical research institute , school of medicine , kyung hee university , seoul , korea . we selected two snps in the il1rn gene : [ rs4251961 ( -828 , t > c ) and rs315952 ( ser133ser ) ] . they were searched from the snp database in ncbi ( http://www.ncbi.nlm.nih.gov/snp , db141 ) , and reviewed to select in the exon area and the promoter area . peripheral blood of all subjects were collected in edta blood tube , stored in 20c freezer before the extraction of genomic dna . genomic dna was extracted with roche dna extraction kit ( indianapolis , in , usa ) . polymerase chain reactions ( pcrs ) of the snps were conducted using the following primers in the table 2 to amplify target sequences including these snps [ rs4251961 ( -828 , t > c ) and rs315952 ( ser133ser ) ] . pcr condition was 38 cycles at 94c for 30 sec , 58c for 30 sec , and 72c for 30 sec . each pcr product was analyzed by direct sequencing in order to obtain the genotype of each snp . direct sequencing , sequence sorting , and genetic data were performed by abi prism 3730xl analyzer ( pe applied biosystems , foster city , ca , usa ) and seqmanii software ( dnastar , madison , wi , usa ) . snpstats ( http://bioinfo.iconcologia.net/index.php?-module=snpstats ) and spss 18.0 ( spss inc . , chicago , il , usa ) also were used to obtain odds ratios ( ors ) , 95% confidence intervals ( cis ) , and p values . multiple logistic regression models were applied in the analysis of genotypes ( kim et al . the haplotype analysis in two snps of the il1rn gene was analyzed with haploview 4.2 software ( daly lab , cambridge , ma , usa ) . in the statistical analysis , subjects were recruited among participants who examined a general health check - up program . each subject was calculated body mass index ( bmi ) , systolic blood pressure ( sbp ) , and diastolic blood pressure ( dbp ) . bmi was also used by dividing the subject s mass by the square of height ( kg / m ) . according to the classification of korean society for the study of obesity ( underweight , bmi<18 ; normal , bmi 18 to<23 ; moderately obese , bmi 23 to<25 ; obesity i , bmi 25 to<30 ; obesity ii , bmi30 ) , subjects were divided into two subgroups , the overweigh / obese group ( bmi23 , n=122 ) and the normal group ( 18<bmi<23 , n=123 ) . and overweigh / obese subjects also divided into two subgroups , the overweigh / obese with hypertension group ( > 130 mmhg in sbp/>85 mmhg in dbp , n=40 ) and the overweigh / obese with non - hypertension group ( < 130 mmhg in sbp/<85 mmhg in dbp , n=98 ) . the subjects with severe diseases , such as stroke , diabetic mellitus , and cancers were excluded in this study . ethical approval of this study was obtained from the ethics review committee of medical research institute , school of medicine , kyung hee university , seoul , korea . we selected two snps in the il1rn gene : [ rs4251961 ( -828 , t > c ) and rs315952 ( ser133ser ) ] . they were searched from the snp database in ncbi ( http://www.ncbi.nlm.nih.gov/snp , db141 ) , and reviewed to select in the exon area and the promoter area . peripheral blood of all subjects were collected in edta blood tube , stored in 20c freezer before the extraction of genomic dna . genomic dna was extracted with roche dna extraction kit ( indianapolis , in , usa ) . polymerase chain reactions ( pcrs ) of the snps were conducted using the following primers in the table 2 to amplify target sequences including these snps [ rs4251961 ( -828 , t > c ) and rs315952 ( ser133ser ) ] . pcr condition was 38 cycles at 94c for 30 sec , 58c for 30 sec , and 72c for 30 sec . each pcr product was analyzed by direct sequencing in order to obtain the genotype of each snp . direct sequencing , sequence sorting , and genetic data were performed by abi prism 3730xl analyzer ( pe applied biosystems , foster city , ca , usa ) and seqmanii software ( dnastar , madison , wi , usa ) . snpstats ( http://bioinfo.iconcologia.net/index.php?-module=snpstats ) and spss 18.0 ( spss inc . , chicago , il , usa ) also were used to obtain odds ratios ( ors ) , 95% confidence intervals ( cis ) , and p values . multiple logistic regression models were applied in the analysis of genotypes ( kim et al . , 2014 ; yang , 2013 ) . the haplotype analysis in two snps of the il1rn gene was analyzed with haploview 4.2 software ( daly lab , cambridge , ma , usa ) . in the statistical analysis , table 3 shows the genotype and allele frequencies of two snps ( rs4251961 and rs315952 ) between the normal group and the overweigh / obese group . genotype distributions of two snps in this study were in hardy - weinberg equilibrium in control subjects ( rs4251961 , p=1.00 ; rs315952 , p=0.35 , data not shown ) . frequencies of rs4251961 snp genotype of the il1rn gene in the normal group and the overweigh / obese group were 82.9% : 16.3%:0.8% and 85.2%:14.8%:0.0% ( t / t genotype : t / c genotype : c / c genotype ) . frequencies of rs4251961 snp in the normal group and the overweigh / obese group were 91.1%:8.9% and 92.6%:7.4% ( t allele : c allele ) . frequencies of rs315952 snp genotype of the il1rn gene in the normal group and the overweigh / obese group were 33.3% : 52.9%:13.8% and 32.0%:50.8%:17.2% ( c / c genotype : c / t genotype : t / t genotype ) . frequencies of rs315952 snp in the normal group and the overweigh / obese group were 59.8%:40.2% and 57.4%:42.6% ( c allele : t allele ) . there were differences of the genotype and allele frequencies in the normal group and the over - weigh / obese group . however , the differences did not show any significant association with obesity ( p>0.05 ) . two snps ( rs4251961 and rs315952 ) of the il1rn gene were analyzed for haplotype analysis using haploview 4.2 . there were four haplotypes ( haplotype tc , frequency=0.57 ; haplotype tt , frequency=0.35 ; haplotype ct , frequency=0.07 ; haplotype cc , frequency=0.02 ) ( table 4 ) . the difference between the normal group and the overweigh / obese group also did not show any association with obesity ( p>0.05 ) . in clinical analysis , frequencies of rs315952 snp genotype of the il1rn gene in the overweigh/ obese with the non - hypertension group and the overweigh / obese with hypertension group were 36.7%:45.9%:17.4% and 15.0% : 67.5%:17.5% ( c / c genotype : c / t genotype : t / t genotype ) . in the genotype distribution analysis , the difference of genotype frequency of rs315952 snp showed significant association with hypertension [ or=4.98 , 95% ci=1.7414.19 , p=0.003 in codominant 1 model ( c / c genotype versus c / t genotype ) and or=3.98 , 95% ci=1.4810.74 , p=0.0029 in dominant model ( c / c genotype versus c / t genotype+t / t genotype ) , table 5 ] . in this study , we investigated the relationship between two snps ( rs4251961 and rs315952 ) of il1rn and obesity . the il1 system included several components , such as two agonists , il1a and il1a . the biological effects are exerted via the interleukin 1 receptor , type i ( il1r1 ) . the binding of il1 to il1ri can be inhibited by the endogenous receptor antagonist il1rn . the balance between il1 and il1rn plays an important role in the regulation of immune function ( arend , 2002 ; dinarello , 1991 ; strandberg et al . , 2006 ) . previous study suggested that il1 system was contributed to body fat accumulation in animal experiment . ( 2003 ) showed that increased il1 activity due to il1rn knockout results in resistance to obesity . there were several genetic researches regarding the relationship between il1rn polymorphisms and obesity ( andersson et al . ( 2004 ) investigated that 86 bp tandem repeat ( vntr ) in the intron 2 of il1rn was associated with obesity . the genotype and allele distributions of vntr in il1rn did not show association with obesity . however , andersson et al . ( 2009 ) reported that rs4252041 snp ( 3-untranslated region , utr ) was associated with the primary outcome total fat mass and regional fat mass . we also investigated the relationship between il1rn polymorphism ( rs315952 , ser133ser ) and obesity and found significant association in obesity patients with hypertension . the rs315952 snp of the il1rn gene was investigated in various diseases including metabolic syndrome , systemic lupus erythematosus , ankylosing spondylitis , and osteoarthritis ( meyer et al . , 2014 ; oh et al . , 2010 ; tahmasebi et al . , 2013 . however , the 86 bp vntr in the intron 2 of il-1rn was not associated with essential hypertension in a pakistani pathan population ( khawaja et al . , 2008 ) . in conclusion , we investigated the relationship between two snps ( rs4251961 and rs315952 ) and obesity . one synonymous snp ( rs315952 , ser133ser ) of the il1rn gene was associated with overweight / obesity with hypertension . the result suggested that il1rn may be contributed to the development of obesity with hypertension . however , another cohort and functional studies will be needed to confirm this result in further study .
recent studies demonstrated that interleukin 1 receptor antagonist ( il-1rn ) plays an important role in metabolic effects . to investigate whether il1rn polymorphisms are associated with obesity , two single nucleotide polymorphisms ( snps ) of the il1rn gene [ rs4251961 ( -828 , t > c ) and rs315952 ( ser133ser ) ] 
 were analyzed in 122 overweigh / obese and 123 control subjects . 
 overweigh / obese subjects were classified according to body mass index ( bmi ) . 
 snpstats was used to obtain odds ratios ( ors ) , 95% confidence intervals ( cis ) , and p values . 
 multiple logistic regression models ( codominant1 , codominant2 , dominant , recessive , and log - additive ) were conducted to analyze the genetic data . 
 synonymous snp ( rs315952 ) of the il1rn gene was associated with overweigh / obese with hypertension ( or= 4.98 , 95% ci= 1.7414.19 , p = 0.003 in codominant 1 model and or= 3.98 , 95% ci= 1.4810.74 , p= 0.0029 in dominant model ) . 
 however , another snp ( rs4151961 ) did not show association with overweigh / obese or overweigh / obese with hypertension . 
 these results suggest that exonic snp of il1rn ( rs 315952 , ser133ser ) may be contributed to overweigh / obese with hyper - tension .