the mdc cohort is a population - based prospective cohort including 28,449 
 participants , with baseline data collection conducted throughout the years 
 199196 ( 22 ) .
the study population 
 includes individuals born during 192350 ( 23 ) and living in malm , the third - largest city in sweden , with about 
 295,000 citizens .
the participation rate was approximately 40% ( 24 ) . among mdc participants recruited from november 1991 to 
 february 1994 ( n = 12,445 ) ,
a random 50% was invited to further participate in 
 a carotid artery disease study , the mdc cardiovascular cohort . in total , 6,103 
 individuals underwent a review of their medical history , a physical examination and a 
 laboratory assessment of cardiovascular risk factors ( 22 , 24 , 25 ) .
information on ldl , hdl , and triglyceride 
 fasting blood concentrations was available in 5,363 individuals .
totally , information 
 on diet , fads genotype , and blood lipids was available in 4,943 
 individuals .
after excluding individuals with diabetes mellitus ( self - reported 
 diagnosis or using anti - diabetes medication , n = 123 ) , users of lipid - lowering 
 medication ( n = 117 ) , and those with a history of cardiovascular event 
 ( coronary event or stroke , n = 117 ) , the study sample included 4,635 
 individuals ( 4568 years , 60.3% female ) .
information about the history of 
 cardiovascular event ( coronary event or stroke ) was taken from the national swedish 
 hospital discharge register and the local register of stroke ( 24 ) .
all individuals provided written , informed consent , and 
 the ethics committee of lund university approved the mdc study protocols .
( t / c ) was performed by 
 matrix - assisted laser desorption ionization time - of - flight mass spectrometry on the 
 sequenom mass - array platform ( san diego , ca ) .
genotyping was successful in 5,806 
 ( 96% ) of the 6,055 individuals with dna available and the rs174547 was in 
 hardy - weinberg equilibrium ( p = 0.92 ) .
in addition , 5,490 of 
 the 6,055 individuals , of whom we still have dna available , were additionally 
 genotyped by the taqman allelic discrimination on abi 7900 with a concordance rate 
 for the two methods of 99.2% .
dietary intake was measured by a modified diet history methodology combining a 168 
 item dietary questionnaire , a 7 day menu book and a 1 h diet history interview , 
 especially designed for the mdc study ( 26 ) . 

the 168 item dietary questionnaire covered food items regularly consumed during the 
 past year .
the participants were asked to fill in the frequency of food intake and 
 estimate the usual portion sizes using a booklet with photographic aids .
the 7 day 
 menu book covered cooked lunch and dinner meals , cold beverages ( including alcoholic 
 beverages ) , medications , natural remedies , and dietary supplements used by the 
 participants . to complete the dietary data ,
the participants were interviewed , for 1 
 h about their food choices , food preparation practices , and portion sizes ( by using a 
 more - extensive booklet of photos ) of the food reported in the menu book .
the trained 
 interviewers checked the menu book and questionnaire for very high reported intakes 
 and overlapping information .
the average daily food intake ( grams per day ) was 
 calculated based on the information from the menu book , interview , and questionnaire , 
 and converted into nutrient and energy intakes by using the mdc food and nutrient 
 database , developed from the pc kost-93 of the swedish national food administration 
 ( 26 ) .
the different pufa intakes were converted into the percentage contributed by the 
 specific pufas to total energy intake ( e% ) .
the pufa dietary variables included in 
 this study were : ala ( c18:3-3 ) ; long - chain -3 pufa ( epa 
 [ c20:5-3 ] , docosapentanoic acid [ dpa , c22:5-3 ] , and dha 
 [ c22:6-3 ] ) ; total -3 pufa ( ala , epa , dpa , and dha ) ; total -6 
 pufa ( la [ c18:2-6 ] , -linolenic acid [ c18:3-6 ] , and aa 
 [ c20:4-6 ] ) ; ala to la ratio ( ala / la ) ; total -3 to total -6 pufa 
 ratio ( -3/-6 pufa ) .
the relative validity of the modified diet history method was examined in 105 women 
 and 101 men .
as the reference method , a total of 18 days of weighed food records was 
 collected during 3 consecutive days , every second month for 1 year .
the 
 energy - adjusted correlation coefficients between the modified diet history method and 
 the reference method were in men : 0.22 for ala , 0.23 for la , 0.55 for aa , 0.24 for 
 epa , 0.37 for dpa , and 0.20 for dha . in women ,
the coefficients were 0.58 for ala , 
 0.68 for la , 0.44 for aa , 0.38 for epa , 0.40 for dpa , and 0.27 for dha ( 27 ) .
hdl , triglyceride , and total cholesterol concentrations were determined in overnight 
 fasting blood samples by standard methods at the department of clinical chemistry , 
 university hospital of malm .
ldl concentration was calculated by the friedewald 
 formula : ldl = total cholesterol  hdl  ( triglycerides/2.2 ) 
 ( 24 ) .
for individuals with a triglyceride 
 concentration of more than 400 mg per deciliter ( 4.5 mmol / l ) , ldl was defined as 
 missing ( 25 ) . body mass index ( bmi )
was 
 calculated as weight in kilograms divided by square of height in meters 
 ( kg / m ) .
a self - administered questionnaire was used to determine lifestyle factors including 
 cigarette smoking , alcohol intake , and physical activity habits .
three categories of 
 smoking status were used : current ( including irregular smoking ) , former , and never 
 smokers .
individuals reporting no 
 alcohol consumption during the last year in the questionnaire , which also were zero 
 reporters of alcohol in the 7 day menu book , were categorized as zero consumers of 
 alcohol .
we divided the other study participants alcohol consumption ( grams 
 per day ) into categories with different cutoffs according to gender .
the cutoff 
 levels for females were 5 , 10 , and 20 g of alcohol per day and the cutoff levels for 
 males were 10 , 20 , and 40 g of alcohol per day . the leisure - time physical activity 
 level ( pal ) was calculated from a list of 17 different activities in the 
 questionnaire . the time spent on each activity
was multiplied by an intensity factor , 
 creating a leisure - time physical activity score .
the leisure - time physical activity 
 score was then divided into quintiles , with the same cutoffs for both genders . 

separate categories for smoking , alcohol intake , and leisure - time physical activity 
 were constructed for the subjects with missing data .
statistical 
 significance was set at p < 0.05 , and all p 
 values are 2-sided .
all of the covariates , except season , were differentially 
 distributed between tertiles of total -3 and -6 pufa intake . assuming 
 an additive model , associations with the fads rs174547
( t / c ) 
 genotype categories were investigated using the general linear model adjusted for age 
 and sex ( basic analysis ) , and thereafter , age , sex , and bmi .
interaction between 
 fads genotype and tertiles of dietary intake levels on serum 
 lipid concentrations were studied by introducing a multiplicative factor of genotypes 
 and diet tertiles as continuous variables in addition to these main factors as 
 separate variables .
the interaction analyses were adjusted for potential confounders : 
 age , sex , bmi , season of diet collection ( four categories ) , cigarette smoking , 
 leisure - time physical activity , alcohol intake , and total energy intake . all 
 continuous variables except age were ln - transformed to achieve normal distribution 
 when testing for trend across fads genotype categories and 
 interaction between fads genotype categories and tertiles of dietary 
 intake levels of pufa on ldl , hdl , and triglycerides ; before transformation , a very 
 small amount ( 0.001 g ) was added to -3 pufa intake to handle zero intakes . in sensitivity analyses ,
misreporters 
 of energy intake were identified by comparing the individually estimated pal 
 expressed as the energy expenditure divided by the basal metabolic rate ( bmr ) , with 
 energy intake divided by bmr , further explained elsewhere ( 28 ) .
individuals were defined as misreporters when the ratio of 
 the reported energy intake to bmr was outside the 95% confidence limits of the 
 calculated pal ( i.e. , under- and over - reporters ) .
the mdc cohort is a population - based prospective cohort including 28,449 
 participants , with baseline data collection conducted throughout the years 
 199196 ( 22 ) .
the study population 
 includes individuals born during 192350 ( 23 ) and living in malm , the third - largest city in sweden , with about 
 295,000 citizens .
the participation rate was approximately 40% ( 24 ) . among mdc participants recruited from november 1991 to 
 february 1994 ( n = 12,445 ) ,
a random 50% was invited to further participate in 
 a carotid artery disease study , the mdc cardiovascular cohort . in total , 6,103 
 individuals underwent a review of their medical history , a physical examination and a 
 laboratory assessment of cardiovascular risk factors ( 22 , 24 , 25 ) .
information on ldl , hdl , and triglyceride 
 fasting blood concentrations was available in 5,363 individuals .
totally , information 
 on diet , fads genotype , and blood lipids was available in 4,943 
 individuals .
after excluding individuals with diabetes mellitus ( self - reported 
 diagnosis or using anti - diabetes medication , n = 123 ) , users of lipid - lowering 
 medication ( n = 117 ) , and those with a history of cardiovascular event 
 ( coronary event or stroke , n = 117 ) , the study sample included 4,635 
 individuals ( 4568 years , 60.3% female ) .
information about the history of 
 cardiovascular event ( coronary event or stroke ) was taken from the national swedish 
 hospital discharge register and the local register of stroke ( 24 ) .
all individuals provided written , informed consent , and 
 the ethics committee of lund university approved the mdc study protocols .
the genotyping of the fads rs174547 ( t / c ) was performed by 
 matrix - assisted laser desorption ionization time - of - flight mass spectrometry on the 
 sequenom mass - array platform ( san diego , ca ) .
genotyping was successful in 5,806 
 ( 96% ) of the 6,055 individuals with dna available and the rs174547 was in 
 hardy - weinberg equilibrium ( p = 0.92 ) .
in addition , 5,490 of 
 the 6,055 individuals , of whom we still have dna available , were additionally 
 genotyped by the taqman allelic discrimination on abi 7900 with a concordance rate 
 for the two methods of 99.2% .
dietary intake was measured by a modified diet history methodology combining a 168 
 item dietary questionnaire , a 7 day menu book and a 1 h diet history interview , 
 especially designed for the mdc study ( 26 ) . 

the 168 item dietary questionnaire covered food items regularly consumed during the 
 past year .
the participants were asked to fill in the frequency of food intake and 
 estimate the usual portion sizes using a booklet with photographic aids .
the 7 day 
 menu book covered cooked lunch and dinner meals , cold beverages ( including alcoholic 
 beverages ) , medications , natural remedies , and dietary supplements used by the 
 participants . to complete the dietary data ,
the participants were interviewed , for 1 
 h about their food choices , food preparation practices , and portion sizes ( by using a 
 more - extensive booklet of photos ) of the food reported in the menu book .
the trained 
 interviewers checked the menu book and questionnaire for very high reported intakes 
 and overlapping information .
the average daily food intake ( grams per day ) was 
 calculated based on the information from the menu book , interview , and questionnaire , 
 and converted into nutrient and energy intakes by using the mdc food and nutrient 
 database , developed from the pc kost-93 of the swedish national food administration 
 ( 26 ) .
the different pufa intakes were converted into the percentage contributed by the 
 specific pufas to total energy intake ( e% ) .
the pufa dietary variables included in 
 this study were : ala ( c18:3-3 ) ; long - chain -3 pufa ( epa 
 [ c20:5-3 ] , docosapentanoic acid [ dpa , c22:5-3 ] , and dha 
 [ c22:6-3 ] ) ; total -3 pufa ( ala , epa , dpa , and dha ) ; total -6 
 pufa ( la [ c18:2-6 ] , -linolenic acid [ c18:3-6 ] , and aa 
 [ c20:4-6 ] ) ; ala to la ratio ( ala / la ) ; total -3 to total -6 pufa 
 ratio ( -3/-6 pufa ) .
the relative validity of the modified diet history method was examined in 105 women 
 and 101 men .
as the reference method , a total of 18 days of weighed food records was 
 collected during 3 consecutive days , every second month for 1 year .
the 
 energy - adjusted correlation coefficients between the modified diet history method and 
 the reference method were in men : 0.22 for ala , 0.23 for la , 0.55 for aa , 0.24 for 
 epa , 0.37 for dpa , and 0.20 for dha . in women ,
the coefficients were 0.58 for ala , 
 0.68 for la , 0.44 for aa , 0.38 for epa , 0.40 for dpa , and 0.27 for dha ( 27 ) .
hdl , triglyceride , and total cholesterol concentrations were determined in overnight 
 fasting blood samples by standard methods at the department of clinical chemistry , 
 university hospital of malm .
ldl concentration was calculated by the friedewald 
 formula : ldl = total cholesterol  hdl  ( triglycerides/2.2 ) 
 ( 24 ) . for individuals with a triglyceride 
 concentration of more than 400 mg per deciliter ( 4.5 mmol / l )
body mass index ( bmi ) was 
 calculated as weight in kilograms divided by square of height in meters 
 ( kg / m ) .
a self - administered questionnaire was used to determine lifestyle factors including 
 cigarette smoking , alcohol intake , and physical activity habits .
three categories of 
 smoking status were used : current ( including irregular smoking ) , former , and never 
 smokers .
individuals reporting no 
 alcohol consumption during the last year in the questionnaire , which also were zero 
 reporters of alcohol in the 7 day menu book , were categorized as zero consumers of 
 alcohol .
we divided the other study participants alcohol consumption ( grams 
 per day ) into categories with different cutoffs according to gender .
the cutoff 
 levels for females were 5 , 10 , and 20 g of alcohol per day and the cutoff levels for 
 males were 10 , 20 , and 40 g of alcohol per day .
the leisure - time physical activity 
 level ( pal ) was calculated from a list of 17 different activities in the 
 questionnaire .
the time spent on each activity was multiplied by an intensity factor , 
 creating a leisure - time physical activity score .
the leisure - time physical activity 
 score was then divided into quintiles , with the same cutoffs for both genders . 

separate categories for smoking , alcohol intake , and leisure - time physical activity 
 were constructed for the subjects with missing data .
statistical 
 significance was set at p < 0.05 , and all p 
 values are 2-sided .
all of the covariates , except season , were differentially 
 distributed between tertiles of total -3 and -6 pufa intake . assuming 
 an additive model , associations with the fads rs174547
( t / c ) 
 genotype categories were investigated using the general linear model adjusted for age 
 and sex ( basic analysis ) , and thereafter , age , sex , and bmi .
interaction between 
 fads genotype and tertiles of dietary intake levels on serum 
 lipid concentrations were studied by introducing a multiplicative factor of genotypes 
 and diet tertiles as continuous variables in addition to these main factors as 
 separate variables .
the interaction analyses were adjusted for potential confounders : 
 age , sex , bmi , season of diet collection ( four categories ) , cigarette smoking , 
 leisure - time physical activity , alcohol intake , and total energy intake .
all 
 continuous variables except age were ln - transformed to achieve normal distribution 
 when testing for trend across fads genotype categories and 
 interaction between fads genotype categories and tertiles of dietary 
 intake levels of pufa on ldl , hdl , and triglycerides ; before transformation , a very 
 small amount ( 0.001 g ) was added to -3 pufa intake to handle zero intakes . in sensitivity analyses ,
misreporters 
 of energy intake were identified by comparing the individually estimated pal 
 expressed as the energy expenditure divided by the basal metabolic rate ( bmr ) , with 
 energy intake divided by bmr , further explained elsewhere ( 28 ) .
individuals were defined as misreporters when the ratio of 
 the reported energy intake to bmr was outside the 95% confidence limits of the 
 calculated pal ( i.e. , under- and over - reporters ) .
each c - allele of rs174547 associated with 0.05 mmol / l lower ldl concentration 
 ( p trend = 0.03 , table 1 ) , but not with hdl or triglyceride concentrations 
 ( p trend = 1.00 and p trend = 0.10 , 
 respectively ) in the basic analysis .
bmi was significantly associated with genotype , and 
 when bmi was included as a covariate , a significant association of 0.02 mmol / l higher 
 triglyceride concentration per c - allele was observed ( p trend = 
 0.04 ) .
similar to the basic analysis , the association with ldl concentration remained 
 significant ( p trend = 0.047 ) , and no association with hdl 
 concentration was detected ( p trend = 0.52 ) after adjusting for 
 bmi .
characteristics of the malm diet and cancer cardiovascular cohort 
 individuals by fads1 rs174547 genotype data are median ( inter - quartile range ) or number ( % ) , if not otherwise 
 indicated .
ala , -linolenic acid ; bmi , body mass index ; e% , energy 
 percentage of total energy intake ; la , linoleic acid ; pufa , polyunsaturated 
 fatty acid .
sex , age , diet variables , and ldl , hdl , and triglycerides ( n 
 = 4,635 ) .
bmi ( n = 4,633 ) . fasting glucose ( n = 
 4,624 ) .
no significant interaction was observed 
 between the fads genotype categories and intake levels of total 
 -3 pufas on ldl concentration ( table 
 2 ) .
however , we observed a significant interaction between the 
 fads genotype categories and long - chain -3 pufa intake on ldl 
 concentration ( p = 0.01 ) .
the c - allele was significantly 
 associated with lower ldl among individuals within the lowest tertile of long - chain 
 -3 pufa intake ( 0.14 e% , p < 0.001 ) , but not among those 
 in the mid- ( 0.140.28 e% ) or highest tertiles ( > 0.28 e% ) . when examining 
 within - genotype categories , the high long - chain -3 pufa intake was associated 
 significantly with higher ldl concentration among the cc - genotype ( p 
 < 0.001 ) and tc - genotype carriers ( p = 0.04 ) but not among 
 tt - genotype carriers ( p = 0.17 ) ( fig .
, there was a significant interaction 
 between the fads genotype categories and ala / la intakes on hdl 
 concentration ( p = 0.03 ) despite lack of significant 
 associations between the fads genotypes and hdl concentration in any of 
 the ala / la tertiles .
however , we observed significant associations between ala / la and 
 hdl concentration among cc- ( p = 0.046 ) and tc - genotype carriers 
 ( p = 0.02 ) but not among those with the tt - genotype ( fig .
no significant interactions 
 were observed between the fads genotype categories and any of the 
 different pufa intake levels on triglyceride concentration ( table 2 ) .
association between rs174547 ( t / c ) for each additional c - allele and blood lipids 
 in strata of diet intakes among 4,635 individuals effect size (  ) = difference in lipid concentration for each 
 additional c - allele .
ala , -linolenic acid ; bmi , body mass index ; e% , 
 energy percentage of total energy intake ; la , linoleic acid ; pufa , 
 polyunsaturated fatty acid . adjusted for age and sex .
adjusted for age , sex , season , alcohol intake , cigarette smoking , leisure time 
 physical activity , bmi , and total energy intake .
association between rs174547 and ldl in strata of long - chain -3 pufa among 
 4,635 individuals .
the cc - genotype was associated with 0.14 mmol / l lower ldl 
 concentration among individuals with low intakes of long - chain -3 pufa 
 ( 0.14 e% , p = 2.3  10 ) , but 
 not among those with medium ( 0.140.28 e% ) or high ( > 0.28 e% ) intakes 
 ( p = 0.98 and p = 0.86 , 
 respectively ) . a low intake of long - chain -3 pufa was associated with 0.20 
 mmol / l and 0.06 mmol / l higher hdl concentration among individuals with cc - genotype 
 ( p = 2.7  10 ) and tc - genotype 
 ( p = 0.04 ) but not among those with tt - genotype 
 ( p = 0.17 ) .
association between ala / la and hdl in strata of rs174547 among 4,635 individuals . 

a high ala / la was associated with 0.04 mmol / l and 0.02 mmol / l higher hdl 
 concentration among individuals with cc - genotype ( p = 
 0.046 ) and tc - genotype ( p = 0.02 ) but not among those with 
 tt - genotype ( p = 0.96 ) . there was no association between 
 the cc genotype and hdl in individuals with low , medium , or high ala / la 
 ( p = 0.07 , p = 0.35 , and 
 p = 0.35 , respectively ) .
we observed a significant 
 interaction of the fads genotype categories and long - chain -3 
 pufa on ldl concentrations in men ( p = 0.01 ) , but not in women 
 ( p = 0.39 ) .
however , these interactions did not significantly 
 differ between the genders ( p = 0.08 ) , and there was no 
 significant difference in gender distribution across the tertiles of long - chain 
 -3 pufa .
no significant interactions of fads genotype categories 
 and ala / la on the levels of hdl were detected , or any of the different pufa intakes on 
 triglycerides levels , either in men or in women .
there were significantly more males than females in the highest tertiles of total 
 -3 and -6 pufa intake compared with the mid- and lowest tertiles 
 ( p < 0.001 ) . because the gender distribution across the tertiles 
 of -3 and -6 pufa intakes was not equal , we repeated all of the 
 interaction analyses using gender - specific cutoffs for the long - chain -3 and 
 -6 pufa tertiles .
however , the above - reported results remained essentially the 
 same when using gender - specific cutoffs . in sensitivity analyses ,
when excluding suspected misreporters of energy ( 19.3% of the 
 study sample ) , the interaction between the fads genotype categories and 
 long - chain -3 pufa intakes on ldl remained significant ( p 
 = 0.04 ) .
the interaction between the fads genotype categories 
 and ala / la intake levels on hdl cholesterol was slightly attenuated after excluding 
 misreporters ( p = 0.06 ) .
interactions between 
 fads genotype categories and the different pufa intake levels on 
 triglyceride remained nonsignificant .
this study indicates that the dietary intake levels of long - chain -3 pufas may 
 modify the association between fads rs174547 and ldl concentration . 

additionally , the intake levels of ala / la may modify the associated effect of 
 fads genotype categories on hdl concentrations .
although several earlier studies , similar to our results , have found an association 
 between the minor allele of rs174547 ( or an snp in high allelic association ) and 
 decreased ldl concentrations ( 6 , 13 , 2931 ) , some inconsistency 
 between the reported associations with lipids and lipoproteins remains .
( 4 ) demonstrated that the minor c - allele of 
 rs174547 associated with lower hdl and higher triglyceride concentrations in caucasians 
 and similar associations were observed in a japanese population ( 21 ) .
however , because the same c - allele was found to associate 
 significantly with decreased ldl , but not with hdl or triglycerides in a mongolian 
 population , it was suggested that differences in dietary fish intake between japanese 
 and mongolians could provide an explanation of the dissimilar results ( 21 ) .
the mongolian diet is mainly based on 
 livestock products , with a very low intake of fish compared with the japanese diet , 
 which , in general , includes a very large amount of fish products .
consistently , japanese 
 individuals had higher plasma concentrations of -3 pufa and a higher 
 -3/-6 pufa compared with mongolians ( 32 ) . in our study , the rs174547 c - allele was associated with lower ldl 
 concentration only in the lowest intake tertile of long - chain -3 pufa . because 
 the dietary source of long - chain fatty acids mainly comes from fatty fish , our finding 
 is in agreement with the suggestion of nakayama et al .
( 21 ) that among individuals with low fish intake , in our study 
 represented by those in the lowest intake tertile of long - chain pufas , the association 
 between the fads genotype categories and ldl concentrations may be 
 accentuated .
( 13 ) , who reported a 
 significant association between the minor allele of rs174546 ( corresponding to the 
 c - allele of rs174547 of our study ) and lower hdl concentration among individuals with 
 high consumption of -6 pufas ( 5.26 e% ) , we observed no significant 
 interaction between -6 pufa intakes and the fads genotype on hdl 
 concentration .
however , because low intake of -6 pufa could indirectly reflect a 
 high ala / la intake , our observation of interaction between the fads 
 genotype categories and ala / la intakes on hdl cholesterol concentration , as well as 
 association between high ala / la intake and higher hdl concentration among the c - allele 
 carriers , could be in line with findings by lu et al .
fads1 is responsible for the desaturation of ala and la into epa and aa ( 9 , 10 ) . 

( 4 ) demonstrated that the minor allele of rs174547 ( in our study 
 associated with lower ldl concentration ) was associated with lower gene expression of 
 the fads1 and fads3 transcripts .
tanaka et al . ( 31 ) showed that individuals homozygous for the 
 minor allele of an snp in high allelic association with fads rs174547 
 had lower plasma concentrations of aa compared with individuals homozygote for the major 
 allele .
the 
 potential mechanism for association between high ala / la intake and higher hdl among the 
 minor allele carriers could be that the minor allele , which has been associated with a 
 lower desaturase activity ( 14 ) , may affect the 
 availability of long - chain -3 pufas differently between the genotypes .
the 
 metabolic derivatives , eicosanoids , of these long - chain -3 pufas are potent 
 activators of peroxisome proliferator - activated receptors ( 9 , 20 ) , which can regulate 
 the expression of genes directly involved in hdl production ( 13 ) .
therefore , our result may reflect a limited long - chain pufa 
 availability among rs174547 minor allele carriers and thereby association between hdl 
 concentrations and ala / la intake .
the strengths of our study include a relatively large sample size and detailed 
 information on dietary intakes based on a 168 item dietary questionnaire , a 7 day menu 
 book , and a 1 h interview .
however , the estimated dietary intakes were based on 
 self - reports , and the limitation of a short - term diet measurement to reflect the 
  habitual  intake may have introduced misclassification of dietary intakes 
 and attenuation of the associations .
although dietary data from the mdc is in general of 
 very high relative validity ( 33 ) , the relative 
 validity of some pufas is still rather low , especially that of long - chain -3 
 pufas in men , which is a weakness of the current study .
one reason for the low validity 
 may be the infrequent consumption of fatty fish ( major source of long - chain -3 
 pufas ) among many of the study participants . because the fish consumed at main meals was 
 only registered during a limited number of 7 days , misclassification may be a problem . 

furthermore , this is a cross - sectional study , which limits our possibility to 
 investigate causality . finally , we performed multiple tests , and thus some of the 
 observed significant associations and interactions could be due to chance and need to be 
 replicated .
it is generally accepted that genetic and environmental factors influence the blood 
 lipid and lipoprotein concentrations , but very little is known about such interactions . 

our findings suggest that the dietary intakes of different pufas may modify the 
 associated effect of the genetic variation in fads on ldl and hdl 
 concentration .
our results emphasize the importance of dietary fat composition in 
 modifying the effect of genetic susceptibility on blood lipid and lipoprotein 
 concentrations and highlight the potential of developing individualized prevention 
 strategies for dyslipidemia and cardiovascular disease in the future .
however , for such 
 strategies to become possible , a major challenge now is to learn more about the 
 importance and mechanisms of interactions between genetic variants , dietary intakes , and 
 blood lipid concentrations .
it is therefore important to replicate our results in 
 well - powered studies with good - quality dietary data .
 polymorphisms of the fa desaturase ( fads ) gene cluster have been 
 associated with ldl , hdl , and triglyceride concentrations . because fads converts 
 -linolenic acid ( ala ) and linoleic acid into pufas , we investigated the 
 interaction between different pufa intakes and the fads polymorphism 
 rs174547 ( t > c ) on fasting blood lipid and lipoprotein concentrations . 
 we included 
 4,635 individuals ( 60% females , 4568 years ) from the swedish population - based 
 malm diet and cancer cohort . 
 dietary intakes were assessed by a modified diet 
 history method including 7-day registration of cooked meals . 
 the c - allele of rs174547 
 was associated with lower ldl concentration ( p = 0.03 ) . 
 we 
 observed significant interaction between rs174547 and long - chain -3 pufa 
 intakes on ldl ( p = 0.01 ) ; the c - allele was only associated 
 with lower ldl among individuals in the lowest tertile of long - chain -3 pufa 
 intakes ( p < 0.001 ) . 
 in addition , significant interaction was 
 observed between rs174547 and the ratio of ala and linoleic fa intakes on hdl 
 ( p = 0.03 ) . 
 however , no significant associations between 
 the c - allele and hdl were detected within the intake tertiles of the ratio . 
 our 
 findings suggest that dietary intake levels of different pufas modify the associated 
 effect of genetic variation in fads on ldl and hdl 
SUBJECTS AND METHODS
Study population
Genotyping
Dietary information
Other variables
Statistical analysis
RESULTS
DISCUSSION