Genetic Variants Associated with Calorie and Macronutrient Intake in a Genome-Wide Association Study

There has been no genome-wide association study (GWAS) for macronutrient intake as a quantitative trait. To explore genetic loci associated with total calorie and macronutrient intake, genome-wide association data of autosomal single nucleotide polymorphisms (SNPs) from Korean adults were analyzed. We conducted a GWAS in 3,690 men and women aged 40 to 60 years from an urban population-based cohort. At the baseline examination (June 18, 2001 through January 29, 2003), DNA samples of the study subjects were collected and analyzed for genotyping. The information of average daily consumption of total calorie, carbohydrate, protein, and fat was obtained from a semi-quantitative food frequency questionnaire and transformed by natural logarithm for analyses after adjustment of calorie intake. Using multivariate linear regression analysis adjusted for age, sex, and height, we tested for 352,021 SNPs and found weak associations, which do not reach genome-wide association significance, with calorie and macronutrient intake. However, a number of SNPs were found to have potential associations with macronutrient intake; in particular, signals in SORBS1 and those in PRKCB1 were likely associated with carbohydrate and fat intake, respectively. We observed an inverse association between the minor allele of the SNPs in these genes and the amount of consumption of carbohydrate or fat. Our GWAS identified loci and minor alleles weakly associated with macronutrient intake. Because SORBS1 and PRKCB1 are reportedly associated with the metabolism of glucose and lipid as well as with obesity-related diseases, further investigations on biological and functional roles of polymorphism of these genes in the relation to macronutrient intake are warranted.

Relative validities of 3-day food records and the food frequency questionnaire

The food frequency questionnaire (FFQ) has been used as an important dietary assessment tool in epidemiologic studies, but the usefulness of the FFQ has been debated in recent years. This study was performed to evaluate the relative validities of 3-day food records and the semi-quantitative FFQ. A total of 124 subjects finished 3-day food records (FRs) during each of the four seasons, as well as the FFQ from December 2002 to May 2004. The FFQ was a food based semi-quantitative FFQ including 103 items. Three-day FRs from each season and a randomly selected season were compared with the remaining 9-day FRs. The remaining 9-day FRs, as a reference measurement, were also compared with the FFQ. Pearson's correlation coefficients between the 3-day FRs and the 9-day FRs were between 0.14 and 0.56. Pearson's correlation coefficients between the FFQ and the 9-day FRs ranged between 0.07 and 0.41. Average proportions of classification into the same quartiles, adjacent quartiles, and distant quartiles between the 3-day FRs and the 9-day FRs were 35.8%, 40.5%, and 5.2%, respectively. On average, the proportions of classification into the same quartiles, adjacent quartiles, and distant quartiles between the FFQ and the 9-day FRs were 31.1%, 39.4%, and 6.9%, respectively. Three-day FRs showed higher correlations and higher agreement proportions of quartile classification with the 9-day FRs than did the FFQ, but both relative validities of 3-day FRs and the FFQ appear to be acceptable as dietary assessment tools. Further studies for validating food intake by reliable biomarkers are necessary.

Protein Tyrosine Phosphatase N1 Gene Variants Associated with Type 2 Diabetes Mellitus and Its Related Phenotypes in the Korean Population

Protein phosphorylation at tyrosine residues is a key regulatory event that modulates insulin signal transduction. We studied the PTPN1 gene with regard to susceptibility to Korean type 2 diabetes mellitus (T2DM) and its related quantitative traits. A total of seven SNPs [g.36171G>A (rs941798), g.58166G>A (rs3787343), g.58208A>G (rs2909270), g.64840C>T (rs754118), g.69560C>G (rs6020612), g.69866G>A (rs718050), and g.69934T>G (rs3787343)] were selected based on frequency (>0.05), linkage disequilibrium (LD) status, and haplotype tagging status. We studied the seven SNPs in 483 unrelated patients with type 2 diabetes (age: 64+/-2.8 years, onset age: 56+/-8.1 years; 206 men, 277 women) and 1138 nondiabetic control subjects (age: 64+/-2.9; 516 men, 622 women). The SNP rs941798 had protective effects against T2DM with an odds ratio of 0.726 (C.I. 0.541~0.975) and p-value=0.034, but none of the remaining six SNPs was associated with T2DM. Also, rs941798 was associated with blood pressure, HDL cholesterol, insulin sensitivity. rs941798 also has been associated with T2DM in previous reports of Caucasian-American and Hispanic-American populations. This is the first report that shows an association between PTPN1 and T2DM in the Korean as well as Asian population.

Dietary Patterns and Prevalence Odds Ratio in Middle-aged Adults of Rural and Mid-size City in Korean Genome Epidemiology Study

Recently, dietary pattern analysis was emerged as an approach to examine the relationships between diet and risk of chronic diseases. This study was to identify groups with population who report similar dietary pattern in Korean ge-nome epidemiology study (KoGES )and association with several chronic diseases. The cohort participants living in Ansung and Ansan (Gyeonggi province )were totally 10,038. Among those, 6,873 subjects with no missing values in food frequency questionnaire were included in this analysis. After combining 103 food items into 17 food groups, 4 dietary factors were obtained by factor analysis based on their weights. Factor 1 showed high factor loadings in vege-tables, mushrooms, meats, fish, beverages, and oriental-cereals. Factor 2 had high factor loadings in vegetables, fruits, fish, and factor 3 had high factor loadings in cereal-oriental, cerial-western and snacks. Factor 4 showed positive high factor loadings in rice and Kimchi and negative factor loadings in mushrooms and milk and dairy products. Using factor scores of four factors, subjects were classified into 3 clusters by K-means clustering. We named those 'Rice and Kimchi eating' group, 'Contented eating' group, and 'Healthy and light eating' group depending on their eating cha-racteristics. 'Rice and Kimchi eating' group showed high prevalence in men, farmers and 60s. 'Contented eating' group and 'Healthy and light eating' group had high prevalence in women, people living in urban area (Ansan Citizen ), with high-school education and above, and a monthly income of one million won and more. 'Contented eating' group appeared lower distribution proportion in the sixties and 'Healthy and light eating' group does higher in the fifties. 'Contented eating' versus 'Rice and Kimchi eating', odds ratio for hypertension, diabetes, metabolic syndrome and obesity significantly decreased after adjusting age and sex (OR =0.64, 0.73, and 0.85 respectively, 95% CI ). Although our results were from a cross-sectional study, these imply that the dietary patterns were related to diseases.

Seasonal Variation of Food Intake in Food Frequency Questionnaire among Workers in a Nuclear Power Plant / 예방의학회지

OBJECTIVES: This study was conducted to investigate the systematic error, such as seasonal change or inadequate food items, in a food frequency questionnaire administered to workers in a Nuclear Power Plant, Korea. METHODS: We performed three repeat-tests with 28 subjects on May 13, July 8 and Dec 16, 1992. Our food frequency questionnaire (FFQ) comprised 84 foods organized into 7 food-groups, and was composed of the items of usual intake frequency (8 categories) and the amount per intake (3 or 4 categories) over the previous year. We compared the means of intake frequency and the frequency of the portion-size according to each season using Repeated Measures ANOVA and Pearson's chisquare test with Fisher's exact test. RESULTS: We found the significant seasonal changes of several food items in intake frequency measurement. These items were typical seasonal foods such as mandarin orange, plum and green vegetables, while the single questions consisted of inadequate food items such as thick beef or similar soup and various kimchi products. Significant seasonal changes in portion-size were found in only two items: cooked rice-brown and fresh.frozen fishes. CONCLUSIONS: The systematic errors observed could caused loss of validity in the FFQ. Consideration should be given for seasonal variation in FFQ survey and methodological concerns are needed to improve the quality for measuring usual diet pattern.

The Association of Dietary Patterns with Bone Mineral Density in Middle-aged Women: A Cohort of Korean Genome Epidemiology Study / 대한지역사회영양학회지

Several nutrients are known to affect bone mineral density (BMD). However, these nutrients are combined with food intake and dietary patterns and little is known about the association of dietary patterns and BMD. The objective of this study was to investigate the association of dietary patterns with BMD in Korea Genome Epidemiology Study subjects. Among 2,884 women (40-69 yr) recruited at baseline study (2001), 861 subjects with BMD measurements at baseline and a 4-year follow up study (2005) completed the semi-quantitative food frequency questionnaire. BMD was measured by the Quantitative Ultrasound method. One hundred three food items were combined into 17 food groups and 4 dietary patterns were identified by factor analysis. Cluster analysis using factor score classified each subject into one of three dietary pattern groups named 'Rice and kimchi eating' (n = 617), 'Contented eating' (n = 124), and 'Healthy and light eating' (n = 120). The 'Healthy and light eating' group, characterized by higher intake of fruit, vegetables, fish, milk and dairy products, and younger age, more exercise, higher education, and higher income than other groups. The tibia BMD of the 'Healthy and light eating' group was higher than the other groups after adjusting for the age. After the adjustment for the age BMI and exercise, the 'Healthy and light eating' group showed significantly lower odds of tibia osteopenia/osteoporosis risk compared to the 'Rice and kimchi eating' group both at the baseline [OR(95% CI) : 0.50(0.30-0.84)] and follow-up [OR(95% CI) : 0.59(0.36-0.97)] examinations. The dietary pattern with low calorie and high intakes of fruit, vegetables, fish, milk and dairy products may have beneficial effects on BMD in middle-aged women.

Osteoporosis Prevalence of Radius and Tibia and Related Factors Using Multiple Bone Sites Quantitative Ultrasound Measurement of the Korean Health and Genome Study Cohort Women / 대한지역사회영양학회지

This study was conducted to investigate osteopenia and osteoporosis prevalence of radius and tibia using Quantitative Ultrasound (QUS) and to identify affecting factors of osteoporosis. A total of 4,340 women aged 40 - 69 years, living in Ansung (rural) and Ansan (mid-sized) area, and free of illnesses affecting bone metabolism participated in the community-based cohort study. Among them 4,059 subjects measured radius bone density and 4,089 measured tibia. The T-score threshold, defined as or = 30) were significantly increased. The OR of osteoporosis decreased across increasing quartiles of intakes of Ca, P and Ca/P. Therefore, maintaining normal BMI and increasing Ca intake and Ca/P ratio may have a beneficial effect on bone health of Korean women.

Study on the Associations of Dietary Variety and Nutrition Intake Level by the Number of Survey Days

Due to the common dietary practice of preparing foods in various ways using the same food item, in addition to rather a large number of food items that average Koreans consume, it is difficult to accurately assess the nutritional adequacy. In an effort to identify a reliable means of assessing the nutritional adequacy of Korean adults, we analyzed the association between the scores of dietary diversity (DDS) and dietary variety (DVS), and the quality of nutrient intake as assessed by Nutrient Adequacy Ratio (NAR) and Mean Adequacy Ratio (MAR). A three day-dietary record was obtained from each of 324 inhabitants, aged 40 to 69 years (mean +/- SD, 52.4 +/- 8.7), of a rural area (Ansung) and a mid-sized city(Ansan) of Korea. These individuals were randomly selected among the participants of the Korean Health and Genome Study. The number of consumed foods and food groups were assesses by DDS (scored 1 to 5) and DVS (ranked 30 < or = , 31 - 40, 41 - 50, 51 - 60, and 60 <) over three-day period, respectively. As DDS/DVS increased, mean daily food intakes tended to increase, and NAR/MAR was improved. Thus, DDS and DVS were significantly correlated with the quality of nutrient intake. Over 95% of the subjects scored less than 2 in DDS for the first one-day period, whilst over 62% recorded 4 during the full three-day period (p < .0001). The mean number of consumed food items increased from 24.9 to 44.4 as a function of days of the record period (p < .0001). We also analyzed the association of DDS and DVS with MAR, using regression analysis, controlling age and sex as covariates. For DDS, the adjusted coefficient determination (adj R2) values were 8.7%, 15.8%, 23.3% of MAR, also increasing as a function of the record duration, whereas they were 27.3%, 33.3%, 37.6% for DVS, respectively, demonstrating that NAR/MAR has a better correlation with DVS than DDS. Our data show that DDS, and DVS in particular, are useful parameters for evaluating nutrient intake in the Korean population. Our data also support that one day-dietary records are by no means adequate for accurately describing a wide variety of food choices offered for average Koreans, and that dietary assessment at least for 3 days or longer should be obtained for a reliable evaluation of dietary quality using DDS or DVS.

Validation and Calibration of Semi-Quantitative Food Frequency Questionnaire: With Participants of the Korean Health and Genome Study / 대한지역사회영양학회지

We carried out a validation-calibration study of the food frequency questionnaire (FFQ) that we had previously developed for a community-based cohort of the Korean Genome and Health Study of the Korea National Genome Research Institute. We have collected a total of 254 3-day diet records (DRs) from 400 subjects, 200 each randomly selected from the two study cohorts of Ansung and Ansan. FFQ was administered at the time of cohort recruitment in 2001, and DRs were collected during a two month period from January through February of 2002. The mean age was 52.2 years. Farming for men and housewife for women were the most common occupations. The majority of the subjects had undergone 6~12 years of education. The general characteristics including demographic and other data were not different from the total cohort subjects. Absolute levels of consumed nutrients including total energy (energy), protein, fat, carbohydrate, calcium, phosphorus, sodium, potassium, iron, retinol, carotene, vitamin A, thiamin, riboflavin, niacin and vitamin C were compared. The average of energy intake was not significantly different between the data collected by the 2 methods. However, consumptions of protein and fat were higher in data of DRs, whereas that of carbohydrate was higher in FFQ data. Significant correlation of each nutrient consumption between the data sets was observed (p <0.05) except in the case of iron, while the average correlation coefficient between them was 0.22 ranging from 0.33 for energy to 0.11 for iron. The results of cross classification by quantile for exact classification ranged from 25.2% (carotene) to 35.0% (phosphorus), and from 64.6% (vitamin A) to 76.4% (retinol) for adjacent classification. The proportion of completely opposite classification was 8.1% in average. Calibration slope was estimated by regression and calibration parameters ranged from 0.025 for carotene to 0.423 for niacin. We conclude that the FFQ we have developed is an appropriate tool for assessing the nutrient intakes as ranking exposures in epidemiology studies in view that amounts of consumed nutrients obtained by FFQ were similar to those collected by DRs, that correlations between consumed nutrients collected by these methods were significant, and that classification results were relatively fair. The correlation coefficients, however, were lower than expected, which may be mainly due to the survey season. In fact, any short-term dietary survey cannot accurately reflect the overall dietary intakes that change heavily depending on seasons. Further studies including the analysis of chemical indices would be helpful for the studies of causal relationship between the diet and disease.

Evaluation of Nutrient Intake Quality Over 40 Year-Old People Living in Rural and Suburban Areas / 대한지역사회영양학회지

ABSTRACT To assess the quality of nutrient intake by area of Korean adults, a dietary survey with the 3-day record method was obtained from 324 subjects aged 40 years and older but younger than 70 (52.4 +/- 8.7) living in a rural area (Ansung) and suburban area of a middle-sized city (Ansan). The quality of nutrient intake was assessed by analyzing Nutrient Adequacy Ratio (NAR), Mean Adequacy Ratio (MAR) and Index of Nutritional Quality (INQ). The average daily mean energy intakes were 1,832 kcal for Ansung and 1,842 kcal for Ansan, respectively. Daily intakes of fat for Ansung and Ansan subjects were 40.9 and 40.3 g, and those for protein were 75.1 and 73.1 g, respectively. The overall calorie: protein: fat ratio (CPF) of energy intake was 63 : 17 : 20. Daily mean intakes of protein, fat, calcium, phosphorus, iron, potassium, carotene, sodium, thiamin, and niacin were significantly higher in Ansung residents than in Ansan subjects (p< .05). The average intakes of energy, calcium, vitamin A were lower than Recommend Dietary Allowance (RDA) in both areas. Note, over 30% of the study subjects had less than 75% of RDA of calcium, vitamin A and riboflavin. The MAR was higher in Ansung than Ansan residents (0.86 and 0.85, respectively; p< .05). INQs were over 1 for most nutrients except calcium (0.87), and that of calcium and phosphorus was each significantly higher in Ansung than Ansan subjects. Based on these results, nutrient intake quality of subjects aged 40 to 69 years living in the surveyed rural area is comparable to that of semi-industrialized suburban area in Korea. Dietary deficiency in all of calcium, vitamin A, and riboflavin, however, was a common problem for both rural and suburban residents.