APOE haplotypes are associated with human longevity in a Central Italy population: evidence for epistasis with HP 1/2 polymorphism

BackgroundApolipoprotein E (APOE) functional haplotypes determined by rs429358 and rs7412 SNPs have been extensively studied and found to be one of the most consistent association in human longevity studies. However, the search for longevity-determining genes in human has largely neglected the operation of genetic interactions.MethodsAPOE haplotypes have been determined for 1072 unrelated healthy individuals from Central Italy, 18–106 years old, divided into three gender-specific age classes defined according to demographic information and accounting for the different survival between sexes. The epistasis between APOE haplotypes and Haptoglobin (HP) 1/2 polymorphism was tested according to three-way contingency table analysis by a log-linear model.ResultsAPOE genotype and haplotype distributions differ significantly along the age classes (Genotype: p = 0.014; Haplotype: p = 0.005) with APOE*ε4 genotype status and haplotype displaying negative association (Genotype: O.R. = 0.377, p = 0.002, Haplotype: O.R. = 0.447, p = 0.005). A significant interaction between APOE*ε4 genotype status, HP 1/2 genotype and age classes is reported (p = 0.006).ConclusionAPOE haplotypes are significantly associated with longevity in our population. Of note, HP*1/*1 genotype seems to protects APOE*ε4 carriers from age-related negative selection. Collectively, these results also suggest and claim for further investigations on APOE/HP interaction in other age-related diseases such as Alzheimer's disease, atherosclerosis and Parkinson's disease.     

Haemochromatosis gene (HFE) polymorphisms and migraine: an association study

Several studies have suggested that iron metabolism may be involved in the pathogenesis of migraine. Using a case-control design, we performed an association study in a cohort of Italian migraine patients to evaluate whether a particular allele or genotype of the haemochromatosis gene (HFE) would modify the occurrence and clinical features of the disease. We genotyped 256 migraine patients and 237 healthy age-, sex- and ethnicity-matched controls for the C282Y and H63D polymorphisms of the HFE gene. Phenotype and allele frequencies of both polymorphisms were similarly distributed in migraine patients and controls. The patients carrying the DD genotype of the H63D polymorphism showed a later age at onset of the disease and an increased number of migraine attacks. Our data suggest that the HFE gene is not a major disease gene for migraine. However, the H63D polymorphism of the HFE gene may be considered a modifying genetic factor in migraine.     

Serum 25(OH)D and type 2 diabetes association in a general population: a prospective study

OBJECTIVE This study aimed to examine vitamin D status as a determinant for development of type 2 diabetes and deterioration of glucose homeostasis. RESEARCH DESIGN AND METHODS A random sample of the general population of Copenhagen, Denmark, was taken as part of the Inter99 study. Included were 6,405 men and women aged 30-65 years at baseline (1999-2001), with 4,296 participating in the follow-up examination 5 years later (2004-2006). Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [25(OH)D]. Diabetes was defined based on an oral glucose tolerance test and a glycosylated hemoglobin (HbA(1c)) test. Secondary outcomes included continuous markers of glucose homeostasis. RESULTS The risk of incident diabetes associated with a 10 nmol/L increase in 25(OH)D was odds ratio (OR) 0.91 (95% CI 0.84-0.97) in crude analyses. The association became statistically nonsignificant after adjustment for confounders, with an OR per 10 nmol/L of 0.94 (0.86-1.03). Low 25(OH)D status was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis after adjustment for confounders. Fasting and 2-h glucose and insulin as well as the degree of insulin resistance increased significantly more during follow-up among those with low 25(OH)D levels compared with those with higher levels. CONCLUSIONS Low 25(OH)D status was not significantly associated with incident diabetes after adjustment for confounders. However, it was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis, indicating that low vitamin D status could be related to deterioration of glucose homeostasis.     

Sex difference in the association of serum uric acid with metabolic syndrome and its components: a cross-sectional study in a Chinese Yi population

Objectives: Since the association between serum uric acid (SUA) and metabolic syndrome (MetS) has been reported extensively, it remains unclear whether SUA is associated with MetS and its components in a Chinese Yi population.

Methods: This study recruited 1,903 people (912 men, 991 women) older than 18 years old from the Liangshan region in Sichuan province. Anthropometric measurements and biochemical indexes were measured by a standard protocol. SUA levels were divided into four quartiles by sex.

Results: The prevalence of hyperuricemia and MetS is 21.0% and 17.1%, respectively. The levels of SUA were positively correlated with waist circumference, body mass index and triglycerides while negatively correlated with high-density lipoprotein cholesterol in both sexes. Increased SUA levels were accompanied with prevalence of MetS and several components in both sexes (P < 0.05). Men with the highest SUA quartile had an increased risk of MetS [OR (95% CI): 3.101 (1.281–7.504)], and men with higher SUA levels had an increased risk of central obesity, high blood pressure and hypertriglyceridemia compared to the lowest SUA quartile. Women with higher SUA levels had an increased risk of MetS, central obesity, hypertriglyceridemia and a lower risk of high blood pressure compared to the lowest SUA quartile.

Conclusions: SUA levels were closely associated with MetS and several components by sex in Chinese Yi population.     

The novel association between red complex of oral microbe and body mass index in healthy Japanese: a population based cross-sectional study

Microbiota has been thought to be one of important environmental factors for obesity or Type 2 diabetes mellitus. Among oral microbe, Porphyromonas gingivalis, Treponema denticola and Tannellera forsythia are known as risk factors, so called red complex, for periodontitis. Red complex could also be a risk factor for obesity. However, recent study indicated that obesity was not improved by periodontal therapy. Thus, we performed a cross sectional study to reveal the association of oral microbe with body mass index in a healthy population. Healthy individuals were randomly recruited. The infections of oral microbe were identified by Taqman polymerase chain reaction. The relationships between number of red complex and body mass index or waist circumference were analyzed. Two hundred and twenty-two apparently healthy Japanese were enrolled. BMI and waist circumference as well as age, periodontitis, number of brushing teeth were significantly associated with the number of red complex after adjusting covariance. The effect size of body mass index or waist circumference was 0.023 (p = 0.028) or 0.024 (p = 0.024), respectively. Body mass index and waist circumference were independently associated with the number of red complex among apparently healthy Japanese. The current observation implies the possibility that oral microbe was associated with obesity in healthy population.     

Smoking status, obesity and hypertension in a general population sample: a cross-sectional study

BACKGROUND: In some studies, hypertension is more common in never and former smokers than in current smokers. AIM: To examine the associations between hypertension and smoking status, when divided into subgroups by overweight and obesity. DESIGN: Cross-sectional study. METHODS: We used data from a national health survey with a probability sample of the national population of Germany aged 18 to 79 (n = 6903 with complete data). Smoking status data were collected via questionnaire. Obesity and overweight were assessed by body mass index, hypertension by blood pressure measurement and by participants' statements about antihypertensive treatment. Analyses were adjusted for gender, age, history of coronary artery disease, serum cholesterol levels, alcohol drinking, exercise, and education. RESULTS: Obese former smokers who were abstinent for 3 or more years had an adjusted odds ratio (OR) 3.6 (95% confidence interval, CI 2.3-5.7) for mild hypertension (> or =140 mmHg systolic or > or =90 mmHg diastolic blood pressure) and an adjusted OR 6.5 (95%CI 3.6-11.8) for moderate or severe hypertension (> or =160 mmHg systolic or > or =100 mmHg diastolic). Normal weight never or former smokers did not differ from normal weight current smokers smoking > or =15 cigarettes/day with regard to likelihood of hypertension (normal weight never smokers, OR 1.1, 95%CI 0.8-1.5; normal weight former smokers, abstinent 3 or more years, OR 0.8, 95%CI 0.5-1.3). DISCUSSION: In this nationally representative sample, never or former smoking was unrelated to hypertension among normal weight individuals.     

Awareness of hypertension and depressive symptoms: a cross-sectional study in a primary care population

Objective: To investigate the association of hypertension awareness and depressive symptoms, and to analyse factors predisposing aware hypertensives to depressive symptoms.

Design: Cross-sectional study in a primary care population.

Setting: Cardiovascular risk factor survey in two semi-rural towns in Finland.

Subjects: Two thousand six hundred seventy-six middle-aged risk persons without an established cardiovascular or renal disease or type 2 diabetes.

Main outcome measures: Depressive symptoms, previous and new diagnosis of hypertension.

Results: Hypertension was diagnosed in 47.9% of the subjects, of whom 34.5% (442/1 282) had previously undetected hypertension. Depressive symptoms were reported by 14% of the subjects previously aware of their hypertension, and by 9% of both unaware hypertensives and normotensive subjects. In the logistic regression analysis, both the normotensive (OR 0.62, 95% CI 0.45–0.86) (p?=?0.0038) and the unaware hypertensive subjects (OR 0.54, 95% CI 0.35–0.84) (p?=?0.0067) had lower risk for depressive symptoms than the previously diagnosed hypertensives. Among these aware hypertensives, female gender (OR 3.61, 95% CI 2.06–6.32), harmful alcohol use (OR 2.55, 95% CI 1.40–4.64) and obesity (OR 2.50, 95% CI 1.01–6.21) predicted depressive symptoms. Non-smoking (OR 0.57, 95% Cl 0.33–0.99) and moderate leisure-time physical activity compared to low (OR 0.53, 95% CI 0.33–0.84) seemed to buffer against depressive symptoms.

Conclusion: Depressive symptoms are common in hypertensive persons even without comorbidities, if the person is already aware of his/her hypertension. Many modifiable, lifestyle associated factors may contribute to the association of hypertension and depressive symptoms.

• Key Points

• Hypertension and depressive symptoms are known to form a toxic combination contributing even to all-cause mortality.

• Comorbidities or the labelling effect of the diagnosis of hypertension can confound their association.

• Our study shows that depressive symptoms are common in hypertensive persons even without comorbidities, if the person is already aware of his/her hypertension.

• Many modifiable, lifestyle-associated factors may contribute to the association of hypertension and depressive symptoms.

• When treating hypertensive patients, consideration of depressive symptoms is important in order to promote favorable lifestyle and control of hypertension.

     

The association of red meat consumption and mental health in women: A cross-sectional study

ObjectivesPrevious studies have shown that red meat consumption has beneficial effects on health. The purpose of this study was to determine the relationship between red meat consumption and depression, anxiety and psychological distress in Tehrani women.MethodsIn this cross-sectional study, 482 women aged 20-50 years old referred to the health centers of Tehran University of Medical Sciences in 2018 were selected by multistage cluster sampling. The usual dietary intake was evaluated using a semi-quantitative food frequency questionnaire containing 168 items that its validity and reliability were approved previously. The red meat category was defined as the sum of red meats (beef, lamb), and organ meats (beef liver, kidney, and heart, ruminant meat). Psychological disorders were assessed using a validated Depression, Anxiety, Stress Scales (DASS) questionnaires with 21-items. In the logistic regression analysis, the results were adjusted to the confounding factors.ResultsThe mean age of the study participants was 31.87 ± 7.6 years. The prevalence of depressive symptoms, anxiety and psychological distress among participants was 34%, 40% and 42%, respectively. After controlling for potential confounders, women in the highest quartile of red meat had a highest prevalence of depressive symptoms (OR: 2.51; 95% CI: 1.32–4.76; p = 0.002), anxiety (OR: 1.82; 95% CI: 1.00–3.29; p = 0.034) and stress (OR: 3.47; 95% CI: 1.88–6.42; p < 0.001) compared with those in the lowest quartile.ConclusionsWe found a significant association between red meat intake and mental health in women. Prospective studies are needed to confirm these findings.     

Relationship between lifestyle factors and hyperhomocysteinemia in general Chinese population: a cross-sectional study

Objectives: Hyperhomocysteinemia (Hhcy) is a known cardiovascular disease (CVD) risk factor. Observational studies had supported the role of lifestyle factors such as physical activity, diet and alcohol consumption in CVD prevention. Our study aimed to determine the relationship between Hhcy and lifestyle factors in general Chinese population.

Methods: In this cross-sectional study, a total of 7135 adults (3320 men and 3815 women) aged 35 years or older were recruited from the rural Northeast China. Data on lifestyle factors, such as physical activities, sleep duration, current smoking and drinking status, dietary habits and familial factors were collected in interviews and laboratory examinations were performed by well-trained personnel.

Results: Plasma total homocysteine (tHcy) level was higher in men than in women, and greater in the elderly than in other age groups. Subjects with Hhcy were more likely to be current smokers (men: OR 1.328, 95% CI 1.143–1.543, p<0.001; women: OR 1.465, 95% CI 1.214–1.767, p<0.001). Separately, men with Hhcy were more likely to have an education of primary school or below (OR 1.251, 95% CI 1.068–1.465, p=0.006) and less likely to eat more vegetables (OR 0.927, 95% CI 0.863–0.996, p=0.037) than the normal-tHcy participants. In women, participants with Hhcy were more likely to have longer sleeping time (>9h/d) (OR 1.677, 95% CI 1.292–2.177, p<0.001), low physical activity (OR 1.721, 95% CI 1.197–2.475, p=0.044) and increased diet score (OR 1.126, 95% CI 1.007–1.259, p=0.037) and less likely to be current drinkers (OR 0.488, 95% CI 0.297–0.802, p=0.005) than the normal-tHcy participants.

Conclusion: Our study revealed that physical activity and current drinking status were not significantly associated with Hhcy in males, but inversely associated in females. In both genders, current smoking status and dietary habits were significantly associated with Hhcy. Our study supports existing recommendations for Chinese to maintain a physically active behaviors and healthy lifestyle habits.     

The association between shift duty and abnormal eating behavior among nurses working in a major hospital: A cross-sectional study

Background

Shift work induces stress, disturbs family life and interrupts regular meal schedules. Few studies have addressed the association between shift duties and abnormal eating behavior among hospital nurses.

Objectives and design

We tested the hypothesis that shift duties were independent predictors of abnormal eating. Self-administered surveys consisting of socio-demographic data, working pattern, Perceived Organizational Support (POS) questionnaire and the patterns of eating style identified by the Dutch Eating Behavior Questionnaires (DEBQ) were used.

Settings

One major acute hospital in one Territory of Hong Kong.

Participants

All 662 nurses who worked on a full-time basis in this hospital were invited to join the study and among them, 378 completed surveys were collected with a response rate of 57.1%. The average age was 37.2 years, and 91.5% were female. 67.3 were registered nurses, 17.9% enrolled nurses; and 14.5% were ranked nursing officers or above. 39.1% worked in acute settings (medical wards, intensive care units and emergency departments), and 62.1% of respondents had at least 11 years of clinical experience and 76.2% of respondents had shift duties with 81.9% having at least four shift duties per month. Only 66.7% of respondents had normal body mass index (BMI 18.5-22.9 kg/m²).

Methods

Three binary logistic regression analyses were conducted with abnormal emotional, external and restraint DEBQ as outcome variables, respectively. We controlled for age, gender, marital status, work setting (acute vs. non-acute), years of clinical experience, the frequency of shift duties, body mass index, perception of body weight changes in the past 6 months, self-perception of recent overeating and POS.

Results

The proportions of participants having abnormal emotional, external and restraint DEBQ scores were 66.4%, 61.4% and 64.0%, respectively. From multiple regression analysis, nurses having 4 or more shift duties per month were more likely to present with abnormal emotional (adjusted odds ratio aOR 2.91, 95% C.I. 1.57-5.42, p = 0.001) and restraint (aOR 3.35, 95% C.I. 1.76-6.38, p < 0.001) DEBS scores.

Conclusions

Shift duties were positively associated with abnormal eating behavior among nurses working in hospitals. More health promotional initiatives should be targeted towards hospital nurses whose duties require frequent night shifts to enhance healthy eating.     

中国汉族人群HLA-DM多态性与强直性脊柱炎疾病关联分析

目的比较中国汉族人群强直性脊柱炎(AS)与健康对照HLA-DMA/HLA-DMB各SNP位点及等位基因多态性,分析可能的AS疾病易感位点及基因。方法选取110名AS患者和1 000名健康无关献血者,利用Taq-Man PCR技术对7个DMA和DMB SNPs(single nucleotide polymorphisms)位点进行了基因分型,运用SPSS软件及Arlequin3.1软件统计基因频率和单体型相关参数。结果 AS组DMA*01∶02基因频率(19.55%)显著低于对照组(28.05%),AS组DMA*01∶02-DMB*01∶01单体型频率(17.51%)也显著低于对照组(26.87%);AS组与对照组DMA p496和DMB p590 SNP位点多态性、DMA*01∶02等位基因以及DMA*01∶02-DMB*01∶01单体型分布差异有统计学意义(P0.05)。结论 DMA*01∶02等位基因和DMA*01∶02-DMB*01∶01单体型可能对于AS疾病具有保护性作用,未来有必要在其他人群中进一步确认并研究其基因功能。     

Association between ventricular repolarization variables and cardiac diastolic function: A cross-sectional study of a healthy Chinese population

BACKGROUND Diastolic electromechanical couple, a well-described phenomenon in symptomatic heart failure, has not been well studied in healthy people. We hypothesized that ventricular repolarization variables, such as the QT interval,Tpeak-to-Tend(Tpe) interval and Tpe/QT ratio, are associated with cardiac diastolic function in the healthy Chinese population.AIM To assess the relationship between ventricular repolarization variables and cardiac diastolic function in apparently healthy Chinese individuals.METHODS This was a community-based cross-sectional study conducted in Shenyang,China. A total of 414 healthy subjects aged 35-91 years were enrolled. All subjects underwent standard 12-lead electrocardiography(ECG) and comprehensive echocardiography. ECG enabled the measurement of QT and Tpe intervals and Tpe/QT ratio. echocardiographic parameters, such as the ratio of mitral early diastolic inflow velocity(E) and late diastolic inflow velocity(A), E-wave deceleration time, left atrial volume(LAV) and LAV index, were measured to assess diastolic function. E/A < 0.75 was considered to indicate reduced diastolic function. ECG and echocardiography results were analyzed separately and in a blinded fashion. Correlation and regression analyses were applied to determine associations.RESULTS Ventricular repolarization variables, such as the QTc interval(393.59 ± 26.74 vs403.86 ± 33.56; P < 0.001), Tpe interval(72.68 ± 12.41 vs 77.26 ± 17.86; P < 0.01),Tpec interval(76.36 ± 13.53 vs 83.32 ± 21.25; P < 0.001) and Tpe/QT ratio(0.19 ±0.03 vs 0.20 ± 0.04; P < 0.01), were significantly different between the normal diastolic function group and the reduced diastolic function group. Significant associations were found between repolarization variables and diastolic function.After adjusting for all other possible confounders, the QTc and Tpe_c intervals were significantly associated with the E/A ratio(P = 0.008; P = 0.010). In men, the QTc interval was associated with abnormal diastolic function, and compared to the third QTc tertile, in the second QTc tertile, the odds ratio was 0.257(95%CI:0.102–0.649; P = 0.004).CONCLUSION Repolarization variables are associated with cardiac diastolic function even in healthy people. Moderate levels of the QTc interval exert a protective effect on diastolic dysfunction in men.     

The association of stroke and coronary heart disease: a population study

In a 20-year population-based study (1960 through 1979), we estimated the cumulative probability of (1) the occurrence of stroke after a diagnosis of angina pectoris, (2) the occurrence of stroke after a diagnosis of myocardial infarction, and (3) the occurrence of myocardial infarction or sudden unexpected death after a diagnosis of cerebral infarction. In patients in whom angina had been diagnosed, no significant difference was noted between the observed and the expected probability of stroke throughout 10 years of follow-up. In patients with a diagnosis of myocardial infarction, a significant difference was noted between observed and expected probabilities of stroke at 1 month and at 2 months. This early excess in probability of stroke was especially pronounced in the subgroup of patients with transmural myocardial infarction but not evident in those with subendocardial myocardial infarction. Among patients with a diagnosis of cerebral infarction, the difference between observed and expected probabilities of myocardial infarction or sudden unexpected death was not significant until 5 years after the cerebral infarction and showed no change thereafter.     

Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis

Genetic polymorphisms of human organic anion transporting polypeptides OATP-C (SLC21A6) and OATP-B (SLC21A9) in the Japanese population were analyzed. The allele frequencies of OATP-C*1a, OATP-C*1b (N130D), OATP-C*1c (R152K and D241N), and OATP-C*5 (V174A) were 35.2, 53.7, 0, and 0.7%, respectively, in 267 healthy Japanese subjects. In the OATP-C gene, we found a novel allele called OATP-C*15 possessing two single nucleotide polymorphisms (SNPs), N130D and V174A, simultaneously. The allele frequency of OATP-C*15 was 3.0%. The allele frequencies of OATP-B*1, OATP-B*2 (T392I), and OATP-B*3 (S486F) were 69.1, 0, and 30.9%, respectively. For functional analysis, each OATP-C and OATP-B allele was expressed in human embryonic kidney (HEK293) cells, and the kinetics of uptake of [(3)H]estrone-3-sulfate was determined. In the case of OATP-C alleles, no significant alteration in K(m) or V(max) values of [(3)H]estrone-3-sulfate uptake was observed, even when the V(max) values were corrected for the expression levels of OATP-C protein. In contrast, V(max), corrected with the expression level of OATP-B*3, was decreased to 42.5% of OATP-B*1, whereas the K(m) values were comparable. Since the frequency of the OATP-B*3 allele was high (30.9%) in our subjects, the SNP of S486F may affect the physiological function and/or pharmacological effects of OATP-B substrates in vivo.     

Haptoglobin phenotype and risk of cervical neoplasia: a case-control study

BACKGROUND: Haptoglobin is an acute-phase glycoprotein that influences host response to infections and tumours. The haptoglobin locus is polymorphic with 2 classes of alleles (Hp(1) and Hp(2)) yielding 3 phenotypes: Hp1-1, Hp2-2, and Hp2-1 with structurally and functionally distinct protein products, suggesting that haptoglobin polymorphism may influence susceptibility to infections and cancers. METHODS: We examined the relation between haptoglobin phenotype and high-grade cervical intraepithelial neoplasia (CIN) in a hospital-based case-control study. Cases (n = 307) were women with biopsy-confirmed CIN-2 or CIN-3. Controls (n = 358) were a random sample of women with normal cytology. The PGMY polymerase chain reaction and reverse line blot methods were used for HPV detection and genotyping. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis. RESULTS: Among controls, phenotype distribution corresponded to allele frequencies of 0.39 for Hp(1) and 0.61 for Hp(2) with no significant deviation from the Hardy-Weinberg equilibrium (p=0.66). With all women included in the analysis, the Hp1-1 phenotype was associated with increased risk of CIN (OR contrasting Hp1-1 vs. Hp2-2 = 1.0; 95% CI: 0.6-1.5). However, in analyses restricted to HPV-positive participants, the Hp1-1 phenotype was associated with 2.7-fold (95% CI: 1.0-7.2) higher risk of CIN. CONCLUSIONS: If confirmed, these findings indicate an increased risk of CIN among women with the Hp1-1 phenotype.