Raynaud's phenomenon in the feet of Arctic open-pit miners.

The literature on Raynaud's phenomenon (RP) in the feet is scarce, especially in the occupational setting. The primary aim of our study was to investigate the occurrence of RP in the feet of miners. As part of the MineHealth project, written surveys and clinical examinations were completed by 260 Arctic open-pit miners working in northern Sweden and Norway (participation rate 53.6%). Data on RP were collected using standardised colour charts and questionnaire items. Clinical examination included assessing the perception of vibration and pain in both feet. There were eight women and three men who reported RP in the feet. Four also had RP in their hands but none acknowledged any first-degree relatives with the condition. Nine reported exposure to foot-transmitted vibration and one to hand-arm vibration. Seven showed signs of neurosensory injury in the feet. To conclude, the occurrence of RP in the feet of miners was 4.4%. Most cases with RP in the feet did not report the condition in the hands and were exposed to vibration transmitted directly to the feet. There were no reports of a hereditary component. Most cases with RP in the feet also had clinical findings suggestive of peripheral neuropathy in the feet.

Neurosensory and vascular symptoms and clinical findings in the hands of Arctic open-pit miners in Sweden and Norway - a descriptive study.

This cross-sectional study aimed to describe exposure to cold climate and hand-arm vibration (HAV) as well as neurosensory and vascular symptoms and clinical findings among open-pit Arctic miners. It was based on data from questionnaires and physical examinations, including 177 men and 75 women from two open-pit mines in Sweden and Norway (response rate 54%). Working outdoors or in an unheated building or machine for at least two hours per day was reported by 44% and HAV exposure of the same duration by 10%. Neurosensory symptoms (e.g. reduced perception of touch) in the hands were reported by 47% and Raynaud's phenomenon by 14%. In brief conclusion, the study showed that Arctic miners were commonly exposed to both cold temperatures and HAV. They also reported a broad range of neurosensory and vascular symptoms in their hands and had abnormal clinical findings related to the symptoms. The results emphasise the need for additional preventive measures in this occupational setting.

No Significant Change in MRI Abnormalities or Back Pain Prevalence in the Thoraco-Lumbar Spine of Young Elite Skiers Over a 2-Year Follow-Up.

Background: Young athletes are at increasing risk for spinal column injuries due to overloading the spine with excessive sports activities, with potential development of complications later in life. Purpose: The purpose of this 2-year follow-up study of young elite skiers and non-athletes was to investigate any potential change in the thoraco-lumbar findings on MRI and to outline any change in back pain prevalence with continuing sporting activity and age. Study Design: Longitudinal cross-sectional study. Methods: MRI of the thoraco-lumbar spine was performed on 30 skiers (mean age 20 years, female 43%) and 16 non-athletes (mean age 19, female 75%), available for the 2-year follow-up. The intervertebral discs were evaluated for signal, height, bulge/herniation, and additionally according to Pfirrmann classification, and the endplates were graded according to endplate defect score. Any of the following disc findings was defined as disc degenerative change: reduced signal, reduced height, bulge, or herniation. All participants answered a specific back pain questionnaire. Results: No significant difference in spinal column abnormalities, nor back pain, was found between baseline and 2-year follow-up in neither skiers nor controls. There was significantly higher prevalence of disc degenerative changes in skiers (73%) than in non-athletes (44%, p=0.05). Skiers (63%) had significantly more Pfirrmann grade ≥3 discs compared to non-athletes (25%) (p=0.03). There was no significant difference in number of endplates with score ≥4 between skiers and non-athletes (50% vs 38%, p=0.40) nor in lifetime prevalence of back pain between skiers (46%) and non-athletes (40%). Conclusion: There was no significant change over time of the spinal column MRI abnormalities, nor back pain prevalence, during a 2-year follow-up of skiers and non-athletes. Young skiers had significantly higher prevalence of spine abnormalities compared with non-athletes. There was no significant difference of the back pain lifetime prevalence in skiers compared with non-athletes.

The one-year prevalence of nonspecific back pain in public primary health care establishments among 1.7 million people in western Sweden.

AIM: The one-year prevalence of diagnosed nonspecific back pain in Sweden is not known. Thus, this observational register-based study aimed to evaluate this prevalence by using data from the Region Västra Götaland, inhabiting 1.7 million people. METHODS: Data from 2014 to 2018 were extracted from the VEGA database register. This register holds all health data from the publicly funded health care establishments in Region Västra Götaland. Aggregated data are presented as the one-year prevalence of unique individuals diagnosed with nonspecific back pain (i.e., the ICD-10 code M54). Stratification by health care level, gender, age, and M54 sub-diagnoses were made. FINDINGS: Between 2014 and 2018, the annual prevalence of diagnosed nonspecific back pain in public primary health care increased from 4.8% to 6.0% (26% increase, P < 0.001, CI 25-27%). In 2018, the one-year prevalence was 7.2% among women and 4.8% among men (50% difference, P = 0.001, CI 49-52%). The one-year prevalence increased by age, and the highest figure (11%) was seen in the age group of 80-84. Low back pain, M54.5, was the most common sub-diagnosis. The one-year prevalence was significantly higher (P < 0.001) among women in all the M54 sub-diagnoses. CONCLUSION: The one-year prevalence of diagnosed nonspecific back pain was 6% in public primary health care in 2018 and has increased since 2014. Women were diagnosed considerably more frequently than men. Publicly funded rehabilitation efforts, as well as actions focusing on the prevention of back pain, is probably money well spent.

Hip pain and its correlation with cam morphology in young skiers-a minimum of 5 years follow-up.

BACKGROUND: There is conflicting evidence regarding the association between cam morphological changes and hip pain, and it remains unclear who with cam morphology will develop hip pain and who will not. This study aimed to investigate the correlation between cam morphology, hip pain, and activity level at a 5-year follow-up in young Alpine and Mogul skiers. METHOD: All students (n = 76) at Åre Ski National Sports High School were invited and accepted participation in this prospective study at baseline. Magnetic resonance imaging (MRI) of both hips was conducted to evaluate the presence of cam morphology (α-angle ≥ 55°) and its size alongside the reporting of hip pain, type, and frequency of training by the Back and hip questionnaire, at baseline. After 5 years, the skiers were invited to complete a shortened version of the same questionnaire. RESULTS: A total of 60 skiers (80%) completed the follow-up questionnaire, of which 53 had concomitant MRI data. Cam morphology was present in 25 skiers (47.2%, 39 hips). Hip pain at baseline and at follow-up was reported in 17 (28.3%) and 22 (36.7%) skiers, respectively. No correlations were found between the activity level, the frequency, and the size of cam morphology and hip pain, except for the right hip α-angle at 1 o'clock and hip pain in skiers with cam morphology at baseline (rs = 0.49; P = 0.03) and at follow-up (rs = 0.47; P = 0.04). A total of 73.3% skiers had retired, of which 48% reported this was due to injuries. CONCLUSION: Hip pain was not shown to be correlated, or had a low correlation, with activity level and the presence and size of cam morphology in young skiers on a 5-year follow-up. Based on these results, cam morphology or activity level did not affect hip pain to develop during 5 years of follow-up in young skiers. Furthermore, this study highlights that almost 75% of young elite skiers had retired from their elite career with almost 50% reporting that this was due to injuries sustained from skiing.

Young elite Alpine and Mogul skiers have a higher prevalence of cam morphology than non-athletes.

PURPOSE: To investigate the prevalence of cam morphology in (1) a group of young elite Mogul and Alpine skiers compared with non-athletes and (2) between the sexes. METHOD: The hip joints of 87 subjects [n = 61 young elite skiers (29 females and 32 males) and n = 26 non-athletes (17 females and 9 males)] were examined using MRI, for measurements of the presence of cam morphology (α-angle ≥ 55). RESULTS: The skiers had a significantly higher prevalence of cam morphology compared with the non-athletes (49% vs 19%, p = 0.009). A significant difference (p < 0.001) was also found between females and males, where 22% of the females and 61% of the males had cam morphology. Among the skiers, there was also a significant difference (p < 0.001) between the sexes, where 28% of the females and 68% of the males had cam morphology. This difference between the sexes was not found in the non-athletic group. No significant differences were found between Mogul and Alpine skiers. CONCLUSION: Young male elite skiers have a higher prevalence of cam morphology of the hips compared with non-athletes. LEVEL OF EVIDENCE: II.

Self-reported traffic-related air pollution and respiratory symptoms among adults in an area with modest levels of traffic.

Health effects of traffic-related air pollution (TRAP) concentrations in densely populated areas are previously described. However, there is still a lack of knowledge of the health effects of moderate TRAP levels. The aim of the current study, a population-based survey including 16 099 adults (response rate 33%), was to assess the relationship between TRAP estimates and respiratory symptoms in an area with modest levels of traffic; Telemark County, Norway. Respondents reported respiratory symptoms the past 12 months and two TRAP exposure estimates: amount of traffic outside their bedroom window and time spent by foot daily along a moderate to heavy traffic road. Females reported on average more symptoms than males. Significant relationships between traffic outside their bedroom window and number of symptoms were only found among females, with the strongest associations among female occasional smokers (incidence rate ratio [IRR], 1.75, 95% confidence interval (CI) [1.16-2.62] for moderate or heavy traffic compared to no traffic). Significant relationship between time spent daily by foot along a moderate to heavy traffic road and number of symptoms was found among male daily smokers (IRR 1.09, 95% CI [1.04-1.15] per hour increase). Associations between traffic outside bedroom window and each respiratory symptom were found. Significant associations were primarily detected among females, both among smokers and non-smokers. Significant associations between time spent by foot daily along a moderate to heavy traffic road (per hour) and nocturnal dyspnoea (odds ratio (OR) 1.20, 95% CI [1.05-1.38]), nocturnal chest tightness (OR 1.13 [1.00-1.28]) and wheezing (OR 1.14 [1.02-1.29]) were found among daily smokers, primarily men. Overall, we found significant associations between self-reported TRAP exposures and respiratory symptoms. Differences between genders and smoking status were identified. The findings indicate an association between TRAP and respiratory symptoms even in populations exposed to modest levels of TRAP.

Adolescent elite skiers with and without cam morphology did change their hip joint range of motion with 2 years follow-up.

PURPOSE: To investigate how range of motion of the hips and the lumbar spine are affected by continued elite, alpine skiing in young subjects, with and without a magnetic resonance imaging verified cam morphology, in a 2-year follow-up study. The hypothesis is that skiers with cam morphology will show a decrease in hip joint range of motion as compared with skiers without cam, after a 2-year follow-up. METHOD: Thirty adolescent elite alpine skiers were examined at the baseline (mean age 17.3 ± 0.7 years) and after 2 years. All skiers were examined for the presence of cam morphology (α-angle > 55°) using magnetic resonance imaging at the baseline. Clinical examinations of range of motion in standing lumbar flexion and extension, supine hip flexion, internal rotation, FABER test and sitting internal rotation and external rotation were performed both at the baseline and after 2 years. RESULTS: Skiers with and without cam morphology showed a significant decrease from baseline to follow-up in both hips for supine internal rotation (right: mean - 13.3° and - 10.9° [P < 0.001]; left: mean - 7.6° [P = 0.004] and - 7.9° [P = 0.02]), sitting internal rotation (right: mean - 9.6° and - 6.3° [P < 0.001]; left: mean - 7.6° [P = 0.02] and - 3.3° [P = 0.008]) and sitting external rotation (right: mean - 16.9° and - 11.4° and left: mean - 17.9° and - 14.5° [P < 0.001]) and were shown to have an increased left hip flexion (mean + 8.4° and + 4.6° [P = 0.004]). Skiers with cam were also shown to have an increased right hip flexion (mean + 6.4° [P = 0.037]). Differences were found between cam and no-cam skiers from baseline to follow-up in the sitting internal rotation in both hips (right: mean 3.25°, left: mean 4.27° [P < 0.001]), the right hip flexion (mean 6.02° [P = 0.045]) and lumbar flexion (mean - 1.21°, [P = 0.009]). CONCLUSION: Young, elite alpine skiers with cam morphology decreased their internal rotation in sitting position as compared with skiers without the cam morphology after 2 years of continued elite skiing. LEVEL OF EVIDENCE: II.

The effect of pelvic tilt and cam on hip range of motion in young elite skiers and nonathletes.

BACKGROUND: Current knowledge of the effect of changes in posture and the way cam morphology of the hip joint may affect hip range of motion (ROM) is limited. PURPOSE: To determine the effect of changes in pelvic tilt (PT) on hip ROM and with/without the presence of cam. STUDY DESIGN: This was a cross-sectional study. MATERIALS AND METHODS: The hip ROM of 87 subjects (n=61 young elite skiers, n=26 nonathletes) was examined using a goniometer, in three different seated postures (flexed, neutral, and extended). The hips of the subjects were further subgrouped into cam and no-cam morphology, based on the magnetic resonance imaging findings in the hips. RESULTS: There was a significant correlation between the hip ROM and the seated posture in both extended and flexed postures compared with the neutral posture. There was a significant decrease in internal hip rotation when the subjects sat with an extended posture with maximum anterior PT (p<0.0001). There was a significant increase in internal hip rotation when the subjects sat with a flexed posture with maximum posterior PT (p<0.001). External rotation was significantly decreased in an extended posture with maximum anterior PT (p<0.0001), but there was no difference in flexed posture with maximum posterior PT. The hips with cam morphology had reduced internal hip rotation in all three positions, but they responded to the changes in position in a similar manner to hips without cam morphology. CONCLUSION: Dynamic changes in PT significantly influence hip ROM in young people, independent of cam or no-cam morphology.

No difference in prevalence of spine and hip pain in young Elite skiers.

PURPOSE: To investigate the prevalence between back and hip pain in young Elite skiers. METHODS: Sample group (n = 102), consisted of young Elite skiers (n = 75) and age-matched non-athletes (n = 27), all completed a three-part back and hip pain questionnaire, Oswestry Disability Index and EuroQoL to evaluate general health, activity level, back and hip pain prevalence. RESULTS: No significant differences were shown for lifetime prevalence of back pain in the skiers (50%) compared with controls (44%) (n.s.). Duration of back pain for the skiers showed (30%) > 1 year, whilst (46%) > 5 years. A significant difference was shown with increased Visual Analogue Scale back pain levels for skiers 5.3 (SD 3.1) compared with controls 2.4 (SD 1.9, p = 0.025). No significant differences were shown for lifetime prevalence of hip pain in skiers (21%) compared with controls (8%) (n.s.). CONCLUSION: Young Elite skiers are shown not to have increased lifetime prevalence for back and hip pain compared with a non-athletic control group. LEVEL OF EVIDENCE: II.

Thermal comfort sustained by cold protective clothing in Arctic open-pit mining-a thermal manikin and questionnaire study.

Workers in the Arctic open-pit mines are exposed to harsh weather conditions. Employers are required to provide protective clothing for workers. This can be the outer layer, but sometimes also inner or middle layers are provided. This study aimed to determine how Arctic open-pit miners protect themselves against cold and the sufficiency, and the selection criteria of the garments. Workers' cold experiences and the clothing in four Arctic open-pit mines in Finland, Sweden, Norway and Russia were evaluated by a questionnaire (n=1,323). Basic thermal insulation (Icl) of the reported clothing was estimated (ISO 9920). The Icl of clothing from the mines were also measured by thermal manikin (standing/walking) in 0.3 and 4.0 m/s wind. The questionnaire showed that the Icl of the selected clothing was on average 1.2 and 1.5 clo in mild (-5 to +5°C) and dry cold (-20 to -10°C) conditions, respectively. The Icl of the clothing measured by thermal manikin was 1.9-2.3 clo. The results show that the Arctic open-pit miners' selected their clothing based on occupational (time outdoors), environmental (temperature, wind, moisture) and individual factors (cold sensitivity, general health). However, the selected clothing was not sufficient to prevent cooling completely at ambient temperatures below -10°C.

Range of Hip Joint Motion Is Correlated With MRI-Verified Cam Deformity in Adolescent Elite Skiers.

BACKGROUND: Radiologically verified cam-type femoroacetabular impingement (FAI) has been shown to correlate with reduced internal rotation, reduced passive hip flexion, and a positive anterior impingement test. PURPOSE: To validate how a clinical examination of the hip joint correlates with magnetic resonance imaging (MRI)-verified cam deformity in adolescents. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: The sample group consisted of 102 adolescents with the mean age 17.7 ± 1.4 years. The hip joints were examined using MRI for measurements of the presence of cam (α-angle ≥55°) and clinically for range of motion (ROM) in both supine and sitting positions. The participants were divided into a cam and a noncam group based on the results of the MRI examination. Passive hip flexion, internal rotation, anterior impingement, and the FABER (flexion, abduction, and external rotation) test were used to test both hips in the supine position. With the participant sitting, the internal/external rotation of the hip joint was measured in 3 different positions of the pelvis (neutral, maximum anteversion, and retroversion) and lumbar spine (neutral, maximum extension, and flexion). RESULTS: Differences were found between the cam and noncam groups in terms of the anterior impingement test (right, P = .010; left, P = .006), passive supine hip flexion (right: mean, 5°; cam, 117°; noncam, 122° [P = .05]; and left: mean, 8.5°; cam, 116°; noncam, 124.5° [P = .001]), supine internal rotation (right: mean, 4.9°; cam, 24°; noncam, 29° [P = .022]; and left: mean, 4.8°; cam, 26°; noncam, 31° [P = .028]), sitting internal rotation with the pelvis and lumbar spine in neutral (right: mean, 7.95°; cam, 29°; noncam, 37° [P = .001]; and left: mean, 6.5°; cam, 31.5°; noncam, 38° [P = .006]), maximum anteversion of the pelvis and extension of the lumbar spine (right: mean, 5.2°; cam, 20°; noncam, 25° [P = .004]; and left: mean, 5.85°; cam, 20.5; noncam, 26.4° [P = .004]), and maximum retroversion of the pelvis and flexion of the spine (right: mean, 8.4°; cam, 32.5°; noncam, 41° [P = .001]; and left: mean, 6.2°; cam, 36°; noncam, 42.3° [P = .012]). The cam group had reduced ROM compared with the noncam group in all clinical ROM measures. CONCLUSION: The presence of cam deformity on MRI correlates with reduced internal rotation in the supine and sitting positions, passive supine hip flexion, and the impingement test in adolescents.

Musculoskeletal symptoms and exposure to whole-body vibration among open-pit mine workers in the Arctic.

OBJECTIVES: This cross-sectional questionnaire study was carried out at 4 open-pit mines in Finland, Norway, Russia and Sweden as part of the MineHealth project. The aim has been to compare the prevalence of musculoskeletal symptoms between drivers of mining vehicles and non-drivers. MATERIAL AND METHODS: The mine workers were asked whether they had suffered from any musculoskeletal symptoms during the previous 12 months in specified body regions, and to grade the severity of these symptoms during the past month. They were also asked about their daily driving of mining vehicles. RESULTS: The questionnaire was completed by 1323 workers (757 vehicle drivers) and the reported prevalence and severity of symptoms were highest for the lower back, followed by pain in the neck, shoulder and upper back. Drivers in the Nordic mines reported fewer symptoms than non-drivers, while for Russian mine workers the results were the opposite of that. The daily driving of mining vehicles had no significant association with the risk of symptoms. Female drivers indicated a higher prevalence of symptoms as compared to male drivers. CONCLUSIONS: The study provided only weak support for the hypothesis that drivers of vehicles reported a higher prevalence of musculoskeletal symptoms than non-vehicle drivers. There were marked differences in the prevalence of symptoms among workers in various enterprises, even though the nature of the job tasks was similar. Int J Occup Med Environ Health 2017;30(4):553-564.

The effect of repetitive flexion and extension fatigue loading on the young porcine lumbar spine, a feasibility study of MRI and histological analyses.

BACKGROUND: The biomechanical mechanisms of failure of FSUs have been studied but the correlation of repetitive flexion and extension loadings to the initial phase of fatigue in young FSUs are still not known. The purpose of the study was to examine the fatigue results of low magnitude repetitive flexion and extension loading on porcine lumbar Functional Spinal Units (FSUs) with Magnetic Resonance Imaging (MRI) and histology. METHODS: Eight FSUs were subject to repetitive pivot flexion and eight to extension loading by a protocol of 20 000 cycles at 1 Hz with a load of 700 N. All loaded FSUs (N = 16) were examined with MRI and histology post loading. Three FSUs were examined with MRI as controls. Further three FSUs were non loaded histology controls. RESULTS: Fifteen (94%) of the loaded FSUs have decreased MRI signal in the growth zone of the superior vertebra and 12 (75%) in the inferior vertebrae. Fourteen (88%) FSUs have increased signal in the superior vertebral body. Fourteen (88%) FSUs have a reduced signal in all or any endplate. The histology morphometry displayed that the unstained parts of the epiphyseal growth zone were larger among the loaded FSUs (mean 29% vs 4%) and that the chondrocytes in the endplate and growth zones had abnormal structure and deformed extracellular matrix. CONCLUSION: Repetitive loading of young porcine FSUs in both extension and flexion causes concurrent MRI and histological changes in the growth zones and endplates, which could be a first sign of fatigue and an explanation for the disc, apophyseal and growth zone injuries seen among adolescent athletes.

The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an α-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans.

Perilipin 2 (PLIN2) is the most abundant lipid droplet (LD)-associated protein in nonadipose tissue, and its expression correlates with intracellular lipid accumulation. Here we identified a missense polymorphism, Ser251Pro, that has major effect on protein structure and function, along with an influence on human plasma triglyceride concentration. The evolutionarily conserved Ser251Pro polymorphism was identified with the ClustalW program. Structure modeling using 3D-JigSaw and the Chimera package revealed that the Pro251 allele disrupts a predicted α-helix in PLIN2. Analyses of macrophages from individuals carrying Ser251Pro variants and human embryonic kidney 293 (HEK293) cells stably transfected with either of the alleles demonstrated that the Pro251 variant causes increased lipid accumulation and decreased lipolysis. Analysis of LD size distribution in stably transfected cells showed that the minor Pro251 allele resulted in an increased number of small LDs per cell and increased perilipin 3 protein expression levels as compared with cells carrying the major Ser251 allele. Genotyping of 2113 individuals indicated that the Pro251 variant is associated with decreased plasma triglyceride and very low-density lipoprotein concentrations. Altogether, these data provide the first evidence of a polymorphism in PLIN2 that affects PLIN2 function and may influence the development of metabolic and cardiovascular diseases.

Effects of prolonged exercise on left ventricular mechanical synchrony in long-distance runners: importance of previous exposure to endurance races.

BACKGROUND: Prolonged exercise has been shown to lead to elevated levels of cardiac troponin and altered cardiac function on echocardiography. It is not known if cardiac synchrony is altered by prolonged exercise. The aims of this study were to assess changes in intra-left ventricular mechanical synchrony and circulating levels of cardiac troponin following prolonged exercise and to evaluate the importance of prior exposure to endurance racing. METHODS: Forty-three male participants in a 30-km cross-country race (20 new participants at this event [median, 3 previous endurance races] age matched against 23 repeat participants [median, 31 previous endurance events]) were assessed prospectively 1 to 2 days before and 24 hours after the race using troponin T and Doppler tissue imaging analyzing the standard deviation of time to peak myocardial systolic velocity (T(s)-SD) in a six-basal, six-midventricular segment model measuring myocardial synchrony. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene was also analyzed, as I allele carriers reportedly have superior endurance performance, while the D allele predisposes to renin-angiotensin system-induced cardiac remodeling. RESULTS: Prerace troponin T was undetectable in all runners, and postrace levels were higher in new runners (median, 0.03 microg/L; interquartile range [IQR], 0.01-0.04 microg/L) than in repeat runners (median, 0.01 microg/L; IQR, 0.01-0.02 microg/L) (P = .03). Although new and repeat runners had similar T(s)-SD at baseline (32 msec [IQR, 22-43 msec] vs 34 msec [IQR, 29-45 msec], P = .13), dyssynchrony increased only in new runners (40 msec [IQR, 31-47 msec], P < .001; in repeat runners, median, 38 msec [IQR, 29-43 msec], P = .30; median relative difference, +13% vs +5%, P = .02). ACE genotype distribution was similar in both groups. Multivariate analysis showed that (1) a lack of prior endurance exposure; (2) more copies of the ACE D allele; and (3) lower peak systolic velocity were independent predictors of postrace dyssynchrony (P < .05 for all). CONCLUSION: Prolonged exertion increased ventricular mechanical dyssynchrony in new endurance participants and in ACE D allele carriers. The long-term impact of such changes warrants future study.

Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.

Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.

Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts.

AIMS: We investigated whether polymorphisms in candidate genes involved in lipid metabolism and type 2 diabetes are related to liver fat content. METHODS: Liver fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS) in 302 Finns, in whom single nucleotide polymorphisms (SNPs) in acyl-CoA synthetase long-chain family member 4 (ACSL4), adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2), and the three peroxisome proliferator-activated receptors (PPARA, PPARD, and PPARG) were analyzed. To validate our findings, SNPs significantly associated with liver fat content were studied in two independent cohorts and related to surrogate markers of liver fat content. RESULTS: In the Finnish subjects, polymorphisms in ACSL4 (rs7887981), ADIPOR2 (rs767870), and PPARG (rs3856806) were significantly associated with liver fat content measured with (1)H-MRS after adjusting for age, gender, and BMI. Anthropometric and circulating parameters were comparable between genotypes. In the first validation cohort of approximately 600 Swedish men, ACSL4 rs7887981 was related to fasting insulin and triglyceride concentrations, and ADIPOR2 rs767870 to serum gamma glutamyltransferase concentrations after adjusting for BMI. The SNP in PPARG (rs3856806) was not significantly associated with any relevant metabolic parameter in this cohort. In the second validation cohort of approximately 3000 subjects from Western Finland, ADIPOR2 rs767870, but not ACSL4 rs7887981 was related to fasting triglyceride concentrations. CONCLUSIONS: Genetic variation, particularly in the ADIPOR2 gene, contributes to variation in hepatic fat accumulation in humans.