Identification of a variant associated with adult-type hypolactasia.

Adult-type hypolactasia, also known as lactase non-persistence (lactose intolerance), is a common autosomal recessive condition resulting from the physiological decline in activity of the lactase-phlorizin hydrolase (LPH) in intestinal cells after weaning. LPH hydrolyzes lactose into glucose and galactose. Sequence analyses of the coding and promoter regions of LCT, the gene encoding LPH, has revealed no DNA variations correlating with lactase non-persistence. An associated haplotype spanning LCT, as well as a distinct difference in the transcript levels of 'non-persistence' and 'persistence' alleles in heterozygotes, suggest that a cis-acting element contributes to the lactase non-persistence phenotype. Using linkage disequilibrium (LD) and haplotype analysis of nine extended Finnish families, we restricted the locus to a 47-kb interval on 2q21. Sequence analysis of the complete region and subsequent association analyses revealed that a DNA variant, C/T-13910, roughly 14 kb upstream from the LCT locus, completely associates with biochemically verified lactase non-persistence in Finnish families and a sample set of 236 individuals from four different populations. A second variant, G/A-22018, 8 kb telomeric to C/T-13910, is also associated with the trait in 229 of 236 cases. Prevalence of the C/T-13910 variant in 1,047 DNA samples is consistent with the reported prevalence of adult-type hypolactasia in four different populations. That the variant (C/T-13910) occurs in distantly related populations indicates that it is very old.

Food choices and health during military service: increases in sugar- and fibre-containing foods and changes in anthropometric and clinical risk factors.

OBJECTIVE: To analyse changes in food choices, diet-related risk factors and their association during 6 months of military service. DESIGN: Longitudinal cohort study in Finland, where all men are liable to military service and a clear majority of each age group completes service. Dietary intake data were collected by self-administered questionnaire before and at 6 months of service. Three dietary indices based on food frequencies were developed to characterize the diet: Sugar Index, Fibre Index and Fat Index. Thirteen diet-related risk factors were measured at the beginning and at 6 months of service. SETTING: Military environment, two geographically distinct garrisons. SUBJECTS: Male conscripts aged 18-21 years (n 256) performing military service. RESULTS: During 6 months of service, positive changes concerned more frequent use of fibre-rich foods (P = 0·011), improved body composition (BMI, waist circumference, muscle mass, fat mass and percentage body fat, P ≤ 0·003 for all), decreased systolic blood pressure and increased HDL cholesterol (P < 0·001 for both). Negative changes concerned more frequent use of sugar-rich foods and increased total cholesterol, TAG and blood glucose (P < 0·001 for all). The consumption of fibre-rich foods was inversely associated with anthropometric risk factors at baseline and with sugar-rich foods at both time points. CONCLUSIONS: Despite more frequent consumption of sweet foods, military service with a unified, nutritionally planned diet, a controlled environment and high physical load has a positive effect on conscripts' health risk factors. The negative changes in blood lipids and glucose may reflect more varied free-time eating.

Genetic predisposition for femoral neck stress fractures in military conscripts.

BACKGROUND: Stress fractures are a significant problem among athletes and soldiers and may result in devastating complications or even permanent handicap. Genetic factors may increase the risk, but no major susceptibility genes have been identified. The purpose of this study was to search for possible genetic factors predisposing military conscripts to femoral neck stress fractures. RESULTS: Eight genes involved in bone metabolism or pathology (COL1A1, COL1A2, OPG, ESR1, VDR, CTR, LRP5, IL-6) were examined in 72 military conscripts with a femoral neck stress fracture and 120 controls. The risk of femoral neck stress fracture was significantly higher in subjects with low weight and body mass index (BMI). An interaction between the CTR (rs1801197) minor allele C and the VDR C-A haplotype was observed, and subjects lacking the C allele in CTR and/or the C-A haplotype in VDR had a 3-fold higher risk of stress fracture than subjects carrying both (OR = 3.22, 95% CI 1.38-7.49, p = 0.007). In addition, the LRP5 haplotype A-G-G-C alone and in combination with the VDR haplotype C-A was associated with stress fractures through reduced body weight and BMI. CONCLUSIONS: Our findings suggest that genetic factors play a role in the development of stress fractures in individuals subjected to heavy exercise and mechanical loading. The present results can be applied to the design of future studies that will further elucidate the genetics of stress fractures.

Quality of diet and food choices of Finnish young men: a sociodemographic and health behaviour approach.

OBJECTIVE: Eating habits of Finns have improved dramatically in 40 years. The proportion of fat in the diet has decreased and vegetable and fruit consumption increased. Knowledge of Finnish young men's dietary habits is limited. The aim was to assess food choices and quality of diet among young men and to analyse how background and health behaviour factors explain it. DESIGN: In 2007, data on eating habits, sociodemographic background factors and health behaviours of 17-21-year-old men (n 2905) entering military service were collected by self-administrated questionnaire. Two indexes - core food index (CFI) and extra food index (EFI) - were formed to describe daily and redundant snacking-type eating, respectively. Associations of background factors and health behaviours on the indexes were analysed by general linear modelling. RESULTS: In all, 13 % consumed fruits and berries daily and 8 % consumed vegetables, whereas 24 % consumed pizza and 19 % consumed hamburgers more than once a week. CFI increased with educational level (P < 0.001) and was explained by background and health behaviour (smoking, physical activity and eating breakfast). EFI was inversely associated with BMI (P < 0.001) and explained by health behaviour: (smoking, physical activity, drinking beer and eating breakfast). CONCLUSIONS: These results indicate that in early adulthood, eating habits cluster with other health behaviours among men. In this age group, education is associated with core food but not with extra food eating habits. Furthermore, seasonal variation is seen in both types of eating. When promoting healthy eating, a distinction between core foods and extra foods by using feasible indexes will be helpful in targeting the efforts.

Nutrient intake and food use of Finnish conscripts in garrison, on leave, and in encampment conditions.

BACKGROUND: 80% of Finnish men fill their civic duty and complete military service. Conscripts' dietary habits have been studied limitedly. OBJECTIVE: The aim was to determine conscripts' nutrient intake and food use in garrison, on leave, and in encampment conditions. METHODS: This study examined volunteer conscripts in: (1) garrison and leave conditions (n=47) and (2) encampment conditions (n=31). Data were collected using food diaries. RESULTS: The proportion of energy derived from fat was 32.9% at garrison and 36.5% at encampment and on leave. Saturated fat constituted 12.5 energy % at garrison, 15.0 energy % at encampment, and 15.3 energy % on leave. Sucrose intake was high at encampment (17.7 energy %) and on leave (13.0 energy %). Salt, vitamin, and mineral intakes exceeded national recommendations in all conditions. Fiber intakes did not reach recommendations. CONCLUSIONS: At garrison and encampment, nutrient intakes reached recommendations. In free time, conscripts favored energy-rich nutrient-poor foods, which warrants intervening and dietary education.

Can primary hypolactasia manifest itself after the age of 20 years? A two-decade follow-up study.

OBJECTIVE: The age at manifestation of primary hypolactasia varies between ethnic groups. Many people report experiencing the first symptoms of lactose intolerance at adult age. The purpose of this study was to investigate whether primary hypolactasia can appear after the age of 20 among the Finnish population and to investigate the outcome of different diagnostic methods of lactose maldigestion. MATERIAL AND METHODS: Lactose digestion status was assessed by the lactose tolerance test with ethanol (LTTE) in 42 subjects (38-71 years) who reported having gastrointestinal symptoms after the ingestion of 20 g or less of lactose and who were diagnosed as lactose digesters in earlier studies. Thirteen of the study subjects underwent upper gastrointestinal endoscopy, and 35 gave a blood sample for DNA analysis. RESULTS: Only one of the 42 subjects studied had the genotype C/C(-13910) indicating hypolactasia. Lactase activity was higher in those with the genotype T/T (69.2 U/g protein) than in those with the heterozygous genotype C/T (36.3 U/g protein) (p=0.017). CONCLUSIONS: Although primary hypolactasia normally appears before the age of 20 years, the decline in lactase activity may on rare occasions continue after that age. Genotyping of the C/T(-13910) variant was found to be a reliable diagnostic approach in defining the lactase persistence/non-persistence status of the study subjects.

Low back pain and its risk indicators: a survey of 7,040 Finnish male conscripts.

Studies describing risk indicators of low back pain (LBP) have focused on adults, although the roots of LBP lie in adolescence and early adulthood. The objective of the present study was to assess the lifetime occurrence and risk indicators of LBP in young adult males. The survey sample comprised 7,333 male conscripts (median age 19), of which 7,040 (96%) answered a questionnaire during the first days of their conscription. The outcome was lifetime LBP prompting at least one visit to a physician. Associations between 18 background variables and LBP were analysed by logistic regression. Altogether 894 (12.7%) respondents reported LBP. Health status was a strong determinant of LBP. The strongest individual risk indicators for LBP were having two or more other than back-related diseases diagnosed by a physician during past year (OR 2.0; 95% CI 1.6-2.5), below-average self-perceived health (OR 1.6; 95% CI 1.3-2.0) and use of smokeless tobacco (OR 1.4; 95% CI 1.2-1.7). Socioeconomic status was not associated with LBP and health behaviours only weakly. The strongest risk indicators for LBP were related to health problems. Of the socioeconomic background factors, none were associated with LBP. It is evident that LBP is associated with other health problems as well, indicating that its background may be multifactorial. This presents challenges for prevention programme planning and implementation. Longitudinal cohort studies are urgently needed to enhance understanding of adolescent risk indicators of LBP.

Association between serum 25(OH)D concentrations and bone stress fractures in Finnish young men.

UNLABELLED: Low vitamin D level may predict rickets, osteomalacia, or osteoporosis. We examined serum 25(OH)D concentration as a predisposing factor for bone stress fracture in 756 military recruits. The average serum 25(OH)D concentration was significantly lower in the group with fracture, suggesting a relationship between vitamin D and fatigue bone stress fracture. INTRODUCTION: Low vitamin D level may predict rickets, osteomalacia, or osteoporosis. Fatigue bone stress fracture is one of the most frequently seen types of overuse injuries in athletes and military recruits. An association was recently shown between vitamin D and BMC. A correlation has also been found between low femoral BMD and stress fractures. We measured serum 25(OH)D concentration in a population sample of military recruits to determine if vitamin D is a predisposing factor for fatigue bone stress fracture. MATERIALS AND METHODS: We prospectively followed 800 randomly selected, healthy Finnish military recruits with a mean age of 19 years for developing stress fractures in homogenous circumstances. Blood for serum 25(OH)D concentration was drawn at entry into military service, and the weight, height, body mass index (BMI), muscle strength, and 12-minute running were measured for all subjects. Serum 25(OH)D concentrations were measured with enzyme immunoassay. At end of the 90-day follow-up, 756 subjects completed the study. Subjects without fracture constituted controls. RESULTS: Twenty-two recruits with stress fracture were identified (2.9%), the incidence being 11.6 (95% CI: 6.8-16.5) per 100 person-years. In the final multivariate analysis, the significant risk factor for stress fracture in conscripts was a below median serum 25(OH)D level (75.8 nM), OR being 3.6 (95% CI: 1.2-11.1). No significant associations between BMI (p = 0.255), age (p = 0.216), or smoking (p = 0.851) and bone stress fracture were found in this study population. CONCLUSIONS: A lower level of serum 25(OH)D concentration may be a generally predisposing element for bone stress fractures. Considering the obvious need of additional vitamin D in prevention of stress fractures, the effects of vitamin D fortification of foods and supplementation will be subjects of interest for future research.

Medicine use by Finnish female conscripts during voluntary military service.

OBJECTIVE: The goal was to assess the prevalence of prescribed and nonprescribed medicine use, use predictors, and origin of medicines for Finnish female conscripts during their voluntary military service. METHODS: An anonymous mail survey was conducted in April 1999 among all Finnish female conscripts on duty. RESULTS: Of the respondents (N = 177; response rate, 68%), 61% had used at least one medicine in the 2 weeks preceding the study, 44% prescribed and 31% nonprescribed medicines. Most of the prescribed medicines were provided by Finnish Defence Forces health care, whereas most of the nonprescribed medicines were of civilian origin. The consumption of prescribed and nonprescribed medicines was differently related to respondents' background variables. Common overall medicine use and use of over-the-counter analgesics and stimulants and their association with potentially negative health behaviors may contribute to inappropriate medicine use. CONCLUSION: Finnish female conscripts commonly use prescribed and nonprescribed medicines. The importance of sufficient medication information for female conscripts is emphasized.

Risk factors for clinical stress fractures in male military recruits: a prospective cohort study.

This prospective study was aimed at evaluating risk factors for symptomatic stress fractures among 179 Finnish male military recruits, aged 18 to 20 years. The subjects were studied in the very beginning of the military service of 6 to 12 months in summer. Bone mineral content (BMC) and density (BMD) were measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine and at the hip and heel ultrasound investigation was performed. Blood was sampled for determination of serum total and free testosterone, total and free estradiol, sex hormone-binding globulin (SHBG), procollagen type I N propeptide, total and carboxylated osteocalcin, tartrate-resistant acid phosphatase 5b, 25-hydroxyvitamin D (25-OHD), and intact parathyroid hormone (iPTH), as well as for studying the XbaI and PvuII polymorphisms of the estrogen receptor gene and the CAG repeat polymorphism of the androgen receptor gene. Urine was collected for the determination of N-terminal cross-linking telopeptide of type I collagen. Muscle strength was measured and Cooper's test was performed. Current exercise, smoking, calcium intake, and alcohol consumption were recorded using a questionnaire. During military service, 15 men experienced a stress fracture, diagnosed with X-ray in 14 and with nuclear magnetic resonance in one man. Those who experienced a fracture were taller than those who did not (P = 0.047). The result of Cooper's test was worse in the fracture group than in the non-fracture group (P = 0.026). Femoral neck and total hip BMC and BMD, adjusted for age, weight, height, exercise, smoking, and alcohol and calcium intake were lower (P = 0.021-0.041) for the fracture group. Stress fractures associated with higher iPTH levels (P = 0.022) but not with lower 25-OHD levels. Bone turnover markers as well as sex hormone and SHBG levels were similar for men with and without stress fracture. There was no difference in the genetic analyses between the groups. In conclusion, tall height, poor physical conditioning, low hip BMC and BMD, as well as high serum PTH level are risk factors for stress fractures in male Finnish military recruits. Given the poor vitamin D status of young Finnish men, intervention studies of vitamin D supplementation to lower serum PTH levels and to possibly reduce the incidence of stress fractures are warranted.

Vitamin D status as a determinant of peak bone mass in young Finnish men.

Severe vitamin D deficiency causes rickets, but scarce data are available about the extent to which vitamin D status determines the development of the peak bone mass in young adults. Our aim was to evaluate the prevalence of vitamin D deficiency [serum 25-hydroxyvitamin D (25-OHD) less than the lower limit of the reference range of 20-105 nmol/liter] and the relationship between vitamin D status and peak bone mass among young Finnish men. A cross-sectional study of determinants of peak bone mass with data on lifestyle factors collected retrospectively was performed in 220 young men, aged 18.3-20.6 yr. One hundred and seventy men were recruits of the Finnish Army, and 50 were men of similar age who had postponed their military service for reasons not related to health. Bone mineral content, bone mineral density, and scan area were measured in lumbar spine and upper femur by dual energy x-ray absorptiometry. Serum 25-OHD concentrations were followed prospectively for 1 yr. In July 2000, only 0.9% of the men had vitamin D deficiency, but 6 months later, in the winter, the respective percentage was 38.9%. After adjusting for age, height, weight, exercise, smoking, calcium, and alcohol intake, there existed a positive correlation between serum 25-OHD and bone mineral content at lumbar spine (P = 0.057), femoral neck (P = 0.041), trochanter (P = 0.010), and total hip (P = 0.025). The correlation coefficients for the bone mineral densities at the four measurement sites were 0.035, 0.061, 0.056, and 0.068, respectively. No correlation was found to scan area. We conclude that vitamin D deficiency is very common in Finnish young men in the winter, and it may have detrimental effects on the acquisition of maximal peak bone mass. As in Finland vitamin D supplementation to infants is now stopped at the age of 3 yr, it can be asked whether at our latitude it should be continued from that age onward, not for the prevention of rickets, but as prophylaxis for osteoporosis.

Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans.

A single-nucleotide variant, C/T(-13910), located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T(-13910) variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T(-13910) H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T(-13910) H98 allele (approximately 5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (approximately 1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T(-13910) allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.