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obesity is a growing medical problem in korea ( lee et al . , 2010 ; mak et al . , 2015 ; paik et al . ,
obesity has been known to relate to many other diseases or bad conditions , such as cancer ( goday et al . , 2015 ) ,
stress ( mak et al . , 2015 ) , heavy alcohol drinking ( kim et al . , 2014 ) , and metabolic syndrome , which causes heart diseases ( byeon et al . , 2015 ) .
many factors may affect the development of obesity , however , obesity shows complex relations of genetic and environmental factors ( apalasamy et al .
, 2015 ; doo et al . , 2015 ; ghosh et al . , 2014
many researchers have reported that various cytokines may influence the cellular signals affected by obesity ( kohlgruber et al . , 2015 ; wueest et al . , 2015 ) , among them ,
insulin - like growth factors ( igfs ) are major axis linked to insulin and growth hormone ( gh ) ( coughlin et al .
they are major hormones affecting free fatty acid , plasma glucose , and adipose tissue , and that may show modified profiles in obesity ( oh et al . , 2015 ) .
additionally , igf1 is released in liver by stimulation of gh , and igf1 receptor signal may also affect insulin signal ( garwood et al . , 2015 ) , however , nutrition , exercise , stress , and body mass index ( bmi ) may affect the igf and gh levels ( fontana et al . , 2010 ; glaser et al .
, 2010 ; greer et al . , 2011 ; sherlock et al . , 2007 ; ubertini et al . ,
peet et al . reported igf1 may be associated with beta - cell autoimmunity ( peet et al . , 2015 ) , and salmon et al .
reported that igf1 level may be associated with obesity resistance ( salmon et al . , 2015 ) .
igfs may affect cellular signals through its receptors , the igf1 receptor ( igf1r ) and igf2 receptor ( igf2r ) ( kashyap , 2015 ; zhu et al . , 1997 ) .
igf receptors have genetic variations that can affect various features in humans , such as cause the short syndrome ( prontera et al . , 2015 ) , growth restriction ( begemann et al . , 2015 ) , and cancer responses to the receptor antibody therapies ( cao et al . , 2014 ; lee et al . ,
however , there was no study directly reported on whether or not obesity and igf1r gene or igf2r gene is associated .
therefore , the relationship between obesity and the single nucleotide polymorphisms ( snps ) of igf1r gene and igf2r gene were investigated in this study .
in the present study , a total of 243 subjects were analyzed ( table 1 ) .
these subjects were recruited among participants that examined a general health check - up program .
subjects with severe diseases such as stroke , psychiatric disorders , and cancers were excluded .
the biochemical characteristics of individuals were measured such as fasting plasma glucose , fasted glycated hemoglobin ( hba1c ) , total cholesterol ( tc ) , high - density lipoprotein cholesterol ( hdl - c ) , and low - density lipoprotein cholesterol ( ldl - c ) . body mass index ( bmi )
is calculated as weight ( in kilograms ) divided by the square of height ( in meters ) . 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 abnormal ( overweight / obese ) group ( bmi23 ) and the normal group ( 18<bmi<23 ) .
genomic dnas were extracted by qiaamp dna mini kit ( qiagen , valencia , ca , usa ) .
we selected exonic rs3743262 ( thr766thr ) and rs2229765 ( glu1043glu ) snps of igf1r gene ( cho et al . , 2012 ) and
genotype of each snp was performed by direct sequencing ( macrogen , seoul , korea ) .
conditions of pcr were 35 cycles at 94c for 30 sec , 58c for 30 sec , and 72c for 30 sec , and 1 cycle at 72c for 5 min for the final extension reaction .
seqmanii software ( dnastar , madison , wi , usa ) was used to determine the genotype .
snpstats ( http://bioinfo.iconcologia.net/index.php ) and spss 18.0 ( spss inc . , chicago , il , usa ) were used to determine the odds ratio ( or ) , 95% confidence interval ( ci ) , and p - value .
multiple logistic regression models ( codominant1 , codominant2 , dominant , recessive , and log - additive models ) were applied and age and gender as covariables were adjusted .
when the numbers of subject were below 5 , the p - values were recalculated by fisher s exact test .
in the present study , a total of 243 subjects were analyzed ( table 1 ) .
these subjects were recruited among participants that examined a general health check - up program .
subjects with severe diseases such as stroke , psychiatric disorders , and cancers were excluded .
the biochemical characteristics of individuals were measured such as fasting plasma glucose , fasted glycated hemoglobin ( hba1c ) , total cholesterol ( tc ) , high - density lipoprotein cholesterol ( hdl - c ) , and low - density lipoprotein cholesterol ( ldl - c ) . body mass index ( bmi )
is calculated as weight ( in kilograms ) divided by the square of height ( in meters ) . 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 abnormal ( overweight / obese ) group ( bmi23 ) and the normal group ( 18<bmi<23 ) .
genomic dnas were extracted by qiaamp dna mini kit ( qiagen , valencia , ca , usa ) .
we selected exonic rs3743262 ( thr766thr ) and rs2229765 ( glu1043glu ) snps of igf1r gene ( cho et al . , 2012 ) and rs629849 ( gly1619arg ) and rs1805075 ( asn2020ser ) snps of igf2r gene .
genotype of each snp was performed by direct sequencing ( macrogen , seoul , korea ) .
conditions of pcr were 35 cycles at 94c for 30 sec , 58c for 30 sec , and 72c for 30 sec , and 1 cycle at 72c for 5 min for the final extension reaction .
seqmanii software ( dnastar , madison , wi , usa ) was used to determine the genotype .
chicago , il , usa ) were used to determine the odds ratio ( or ) , 95% confidence interval ( ci ) , and p - value .
multiple logistic regression models ( codominant1 , codominant2 , dominant , recessive , and log - additive models ) were applied and age and gender as covariables were adjusted .
when the numbers of subject were below 5 , the p - values were recalculated by fisher s exact test .
in the control group , the genotype distributions for all snps were in hwe [ rs3743262 ( p=0.33 ) and rs2229765 ( p=0.45 ) snps of igf1r gene and rs629849 ( p=1.00 ) and rs1805075 ( p=0.84 ) snps of igf2r gene ] .
the genotype frequencies of the polymorphisms were compared between the control group and the overweight / obese group by using logistic regression models with adjustment for age and gender .
the genotype distributions of rs3743262 and rs2229765 snps of igf1r gene and rs629849 and rs1805075 snps of igf2r gene in each group were shown in table 2 . among
tested snps in igf1r and igf2r genes , rs629849 snp of igf2r gene showed significant association with obesity [ or=1.86 , 95% ci=1.023.40 , p=0.044 in codominant1 model ( g / g genotype versus g / a genotype ) ; or=1.99 , 95% ci=1.103.57 , p=0.020 in dominant model ( g / g genotype versus g / a genotype+a / a genotype ) ; or=1.93 , 95% ci=1.133.31 , p=0.013 in log - additive model ( g / g genotype versus g / a genotype versus a / a genotype ) ] , respectively . and
allele distribution between the control group and overweight / obese group also showed significant difference ( or=1.93 , 95% ci=1.143.28 , p=0.015 ) .
however , three snps did show any significant association with development of obesity . in haplotype analysis , we analyzed haplotype using haploview 4.2 .
there were four haplotypes ( cg , ta , ca , and tg haplotype ) in igf1r gene and three haplotypes ( ga , gg , and aa haplotype ) in igf2r gene . among haplotypes , aa haplotype in igf2r gene showed significant difference between the control group and the overweight / obese group ( p=0.0138 ) ( table 3 ) .
in the present study result , the two snps ( rs3743262 and rs2229765 ) in igf1r gene did not show any relationship with obesity , also , a snp ( rs1805075 ) in igf2r gene did not showed any relationship .
however , only one snp ( rs629849 ) of igf2r gene was associated with obesity . minor allele frequency ( maf ) of rs629849 in our study was 0.1 in the control group .
significant associations are shown in the allele frequency , co - dominant model , dominant model , and log - additive model , respectively . in all of them , ors were positive in the minor allele ( a ) .
therefore , it suggests that the minor allele  a  of the rs629849 in the igf2r gene may be associated with development of obesity .
igf2r is a multifunctional receptor that possesses binding sites for diverse ligands , including igf2 , retinoic acid , tgf - beta ( tgfb1 ) , urokinase - type plasminogen activator receptor ( upar ) , and mannose-6-phosphate ( m6p ) ( killian et al . , 1999 ) .
additionally , igf2r is involved in lysozyme reaction and cytotoxic t cell apoptosis ( kornfeld et al . , 1989 ;
motyka et al . , 2000 ) . which means igf2r may have wide range of signal transduction , however , le stunff et al .
reported that increased expression of mutated insulin(ins ) and igf2 gene may predispose offspring to postnatal fat deposition ( le stunff et al . , 2001 ) . and rodriguez et al .
reported that certain haplotype composed by the gene region of igf2-ins - thyroid hormone ( th ) is related with obesity ( rodriguez et al . , 2004 ) .
also , igf2-ins region is associated with past famine history in individuals ( tobi et al . , 2009 ) .
interestingly , igf2r has degradation function of igf2 , which is known as mitogen ( yoon et al . , 2012 ) .
rezgui , studied the correlation of  a  allele and receptor function , however , the researchers concluded that it showed no direct effect and they suspected the linkage between other intronic polymorphisms . in previous study , rs629849 of igf2r gene
the authors concluded that  a  homozygote in rs629849 of igf2r gene may modulate igf2 level in sex - specific manner , and it may affect colorectal cancer risk as a mitogen effect of igf2 .
additionally , rs629849 of igf2r gene was associated with advanced stage of oral cancer , that 
the previous research results are , consistent with ours that the minor  a  allele may tribute to the obesity development . in conclusion , though it was marginal relation in this study , we suggest that having 
a  allele of rs629849 of igf2r gene may be associated with development of obesity in the korean population .
the aim of this study is to investigate the relationship between single nucleotide polymorphisms ( snps ) and susceptibility to obesity . 
 a previous study suggested that insulin - like growth factors ( igfs ) may affect obesity and that igfs regulate cellular signals by receptors that include the insulin - like growth factor 1 receptor ( igf1r ) and the insulin - like growth factor 2 receptor ( igf2r ) . in this research , 
 the rs3743262 and rs2229765 snps of igf1r gene and rs629849 and rs1805075 snps of ig - f2r gene were genotyped in 120 overweight and obese patients with a bmi23 kg / m2 ( body mass index ) and 123 healthy controls with a bmi of 18.523.0 kg / m2 . 
 genotyping of each snp was performed by direct sequencing . among 
 tested snps in igf1r and igf2r genes , rs629849 snp of igf2r gene showed significant association with obesity ( or=1.86 , 95% ci=1.023.40 , p=0.044 in codominant1 model ; or=1.99 , 95% ci=1.103.57 , p=0.020 in dominant model ; or=1.93 , 95% ci=1.133.31 , p=0.013 in log - additive model ) . and 
 allele distribution between the control group and overweight / obese group also showed significant difference ( or=1.93 , 95% ci=1.143.28 , p=0.015 ) . in conclusion , these results indicate that rs629849 snp of igf2r might be contributed to development of obesity in the korean population .