A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?

Recently, we showed that homozygosity for the common 677(C-->T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, causing thermolability of the enzyme, is a risk factor for neural-tube defects (NTDs). We now report on another mutation in the same gene, the 1298(A-->C) mutation, which changes a glutamate into an alanine residue. This mutation destroys an MboII recognition site and has an allele frequency of .33. This 1298(A-->C) mutation results in decreased MTHFR activity (one-way analysis of variance [ANOVA] P < .0001), which is more pronounced in the homozygous than heterozygous state. Neither the homozygous nor the heterozygous state is associated with higher plasma homocysteine (Hcy) or a lower plasma folate concentration-phenomena that are evident with homozygosity for the 677(C-->T) mutation. However, there appears to be an interaction between these two common mutations. When compared with heterozygosity for either the 677(C-->T) or 1298(A-->C) mutations, the combined heterozygosity for the 1298(A-->C) and 677(C-->T) mutations was associated with reduced MTHFR specific activity (ANOVA P < .0001), higher Hcy, and decreased plasma folate levels (ANOVA P <.03). Thus, combined heterozygosity for both MTHFR mutations results in similar features as observed in homozygotes for the 677(C-->T) mutation. This combined heterozygosity was observed in 28% (n =86) of the NTD patients compared with 20% (n =403) among controls, resulting in an odds ratio of 2.04 (95% confidence interval: .9-4.7). These data suggest that the combined heterozygosity for the two MTHFR common mutations accounts for a proportion of folate-related NTDs, which is not explained by homozygosity for the 677(C-->T) mutation, and can be an additional genetic risk factor for NTDs.     

Is hypercholesterolemia a risk factor for alzheimer’s disease?

There is considerable attention being given to the association of Alzheimer's disease and cholesterol homeostasis. To that end, some have suggested that elevated cholesterol levels are a risk factor for Alzheimer's disease. If elevated cholesterol is a risk factor for Alzheimer's disease, then it would be expected that patients with Alzheimer's disease would have elevated serum and brain cholesterol levels. Studies were reviewed that have examined cholesterol levels in Alzheimer's patients and control subjects, including prospective studies, and based on that review, the conclusion is reached that the majority of studies do not support elevated cholesterol levels in serum and brain as a risk factor for Alzheimer's disease. Alternative hypotheses are discussed, including cholesterol domains and subgroups of individuals with hypercholesteremia.     

Is polygyny a risk factor for poor growth performance among Tanzanian agropastoralists?

Anthropologists and demographers have devoted considerable attention to testing the fertility-polygyny hypothesis, which posits that polygynously married women have lower fertility than their monogamously married counterparts. Much less attention has been paid to the potential impact of polygynous marriages on the health and well-being of children. The objective of this paper was to assess whether polygynous marital status is a risk factor for poor nutritional status and growth performance among a cohort of young Tanzanian children. Using data collected from both wet and dry season periods, we tested for an association from both cross-sectional and longitudinal perspectives. Despite relatively high nutritional status compared to other agropastoralists and horticultural populations, as well as the presence of various socioecological factors that were expected to mitigate any "costs" to polygynous marriage, we found that among our target population, polygynous marital status is a risk factor for poor growth performance. This association is most pronounced in the wet season, and maintains even after allowing for the potential influences of child age and sex, and household characteristics. These results counter our original expectation, and suggest that polygyny is costly to children in this population; this does not appear to be the result of difference in early child environment or household wealth.     

Chlamydia pneumoniae--an infectious risk factor for atherosclerosis?

Cardiovascular disease, of which atherosclerosis is an important component, is the leading cause of death in the western world. Although there are well-defined risk factors for atherosclerosis, these factors do not account for all incidences of the disease. Because atherosclerotic processes are typified by chronic inflammatory responses, which are similar to those that are elicited by chronic infection, the role of infection in promoting or accelerating atherosclerosis has received renewed attention. This review focuses on the accumulating evidence that chronic infection with Chlamydia pneumoniae, a ubiquitous human respiratory pathogen, might contribute to atherosclerotic lesion progression.     

Is paraoxonase 192 gene polymorphism a risk factor for membranoproliferative glomerulonephritis in children?

We investigated the effects of paraoxonase (PON1) 192 polymorphism on serum PON1 activity and the impact of phenotypic expression on the risk and prognosis of Turkish children with membranoproliferative glomerulonephritis (MPGN). Eighteen children with biopsy-proven Type I MPGN (10 boys, 8 girls) and age-matched 53 healthy controls were included in the study. PCR (polymerase chain reaction), RFLP (restriction fragment length polymorphism) and agarose gel electrophoresis techniques were used to determine the PON1 192 genotype. PON1 activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON1 192 genotype distribution (AA, AB, BB) in MPGN patients were 61.1%, 22.3%, 16.6% and 15.1%, 35.8%, 49.1% in controls, respectively. The frequency of AA genotypes was significantly higher in the MPGN group (0.611) compared with the healthy controls (0.151) (p < 0.001). Although the serum PON1 activity was lower in MPGN patients (103.3 +/- 55.2 U/l) than the healthy controls (130.9 +/- 71.2 U/mol), the difference was not statistically significant (p = 0.0563). In the genotypes of patients and controls classified according to PON1 A/B polymorphism; serum PON1 activities were significantly increased (p < 0.001, ANOVA) in the order of PON1 AA, AB and BB in both MPGN patients (82.4, 91.7 and 173.6 U/l) and healthy controls (85.9, 119.9 and 193.1 U/l), respectively. There was a significant relationship between the poor prognosis and having AA genotype and low PON1 activity. Of the 8 patients with poor prognosis, 7 had genotype AA and the remaining one was AB heterozygote. Our results suggest that homozygosity for the A allele might have an important role on the risk for developing MPGN and may also be associated with the poor prognosis of disease. In conclusion, we suggest that the PON1 activities are affected by PON1 genetic variability in Turkish patients with MPGN.     

Is lipoprotein(A) a risk factor for atherosclerosis of the retinal arteries?

Elevated plasma Lp(a) has been linked to development of coronary artery disease (CAD). There is no data about plasma Lp(a) and atherosclerosis of the retinal arteries. Therefore the purpose of this study was to assess the risk of retinal vessels atherosclerosis conferred by elevated plasma Lp(a) levels in 73 adult males. The results were compared with those in 45 matched apparently healthy males with no retinal vessel changes. The atherosclerotic changes of the retinal vessels were determined by direct ophthalmoscopy and graded (1-4) according to Scheie. Plasma levels of Lp(a) were measured by radial immunodiffusion. The results were compared using chi-square test. Although a very weak correlation between plasma Lp(a) levels and the incidence of retinal atherosclerosis was found, no significant association between the degree of atherosclerotic changes and plasma Lp(a) levels could be proven. Thus it could be concluded that plasma Lp(a) level is not a significant risk factor for atherosclerosis of the retinal arteries.     

Is obesity a risk factor for deep tissue injury in patients with spinal cord injury?

Deep tissue injury (DTI) is a severe form of pressure ulcers that occur in subcutaneous tissue under intact skin by the prolonged compression of soft tissues overlying bony prominences. Pressure ulcers and DTI in particular are common in patients with impaired motosensory capacities, such as those with a spinal cord injury (SCI). Obesity is also common among subjects with SCI, yet there are contradicting indications regarding its potential influence as a risk factor for DTI in conditions where these patients sit in a wheelchair without changing posture for prolonged times. It has been argued that high body mass may lead to a greater risk for DTI due to increase in compressive forces from the bones on overlying deep soft tissues, whereas conversely, it has been argued that the extra body fat associated with obesity may reduce the risk by providing enhanced subcutaneous cushioning that redistributes high interface pressures. No biomechanical evaluation of this situation has been reported to date. In order to elucidate whether obesity can be considered a risk factor for DTI, we developed computational finite element (FE) models of the seated buttocks with 4° of obesity, quantified by body mass index (BMI) values of 25.5, 30, 35 and 40 kg/m². We found that peak principal strains, strain energy densities (SED) and von Mises stresses in internal soft tissues (muscle, fat) overlying the ischial tuberosities (ITs) all increased with BMI. With a rise in BMI from 25.5 to 40 kg/m², values of these parameters increased 1.5 times on average. Moreover, the FE simulations indicated that the bodyweight load transferred through the ITs has a greater effect in increasing internal tissue strains/stresses than the counteracting effect of thickening of the adipose layer which is concurrently associated with obesity. We saw that inducing some muscle atrophy (30% reduction in muscle volume, applied to the BMI=40 kg/m² model) which is also characteristic of chronic SCI resulted in further substantial increase in all biomechanical measures reflecting geometrical distortion of muscle tissue, that is, SED, tensile stress, shear stress and von Mises stress. This result highlights that obesity and muscle atrophy, which are both typical of the chronic phase of SCI, contribute together to the state of elevated tissue loads, which consequently increases the likelihood of DTI in this population.     

Is methylglyoxal a causative factor for hypertension development?

Hypertension is a life-threatening disease that is associated with increased cardiovascular risks. Causes and mechanisms for hypertension development remain poorly understood. Methylglyoxal (MG), a highly reactive molecule, is a metabolite of sugar. Increased circulation and tissue levels of MG have been documented not only in diabetes but also in hypertension. Many recent studies also link MG-induced vascular damage to the pathogenic process of hypertension. As such, an etiological role of MG in hypertension development is proposed.     

Infant male sex as a risk factor for shoulder dystocia but not for cephalopelvic disproportion: An independent or confounded effect?

Background: Shoulder dystocia (ShD) and cephalopelvic disproportion (CPD) share some common risk factors. Whether infant male sex is an independent risk factor for ShD, or if the risk is confounded by other known factors, is uncertain.Objective: The aim of this study was to explore the unconfounded effect of infant male sex on the risk for ShD and its interaction with other risk factors compared with CPD.Methods: A retrospective data analysis was conducted of deliveries in Lamphun Hospital, Lamphun, Thailand. All vaginal deliveries complicated by ShD were collected as ShD cases. All labors terminated by cesarean delivery (CD) due to CPD were collected as CD/CPD cases. Vaginal deliveries that took place immediately before or after the index ShD cases were collected as controls. Multivariable adjusted odds ratios (AORs) for infant male sex and its 95% CI in cases of ShD and CD/CPD were computed by multichotomous logistic regression controlling for other obstetric risks. The effects of maternal height, gestational age, and birth weight on the risk for ShD or CD/CPD among male or female infants was also explored. Stability of the effect of the risk between male and female infants was tested with Chow tests.Results: Thirty-five ShD cases and 199 CD/CPD cases were collected, as were 586 controls. Infant male sex was a significant independent risk factor for ShD (AOR = 5.00; 95% CI, 1.83-13.61; P = 0.002), but not for CD/CPD (AOR = 1.09; 95% CI, 0.75-1.59; P = NS). For CD/CPD, the effects of maternal height, gestational age, and birth weight were similar for male and female infants, but the corresponding effect on ShD was more pronounced in male than in female infants (P < 0.001 for all comparisons).Conclusions: Infant male sex is a risk factor for ShD independent of other known risks. Male sex also amplified the existing effects of short maternal height, extended gestational age, and greater birth weight. If infant sex is known to be male before delivery, the obstetrician may consider avoiding vaginal delivery in mothers who have other strong risks for ShD.     

Is a sedentary lifestyle an independent predictor for hospital and early mortality after elective cardiac surgery?

Objective

This study evaluates whether a sedentary lifestyle is an independent predictor for increased mortality after elective cardiac surgery.

Methods

Three thousand one hundred fifty patients undergoing elective cardiac surgery between January 2007 and June 2012 completed preoperatively the Corpus Christi Heart Project questionnaire concerning physical activity (PA). Based on this questionnaire, 1815 patients were classified as active and 1335 patients were classified as sedentary. The endpoints of the study were hospital mortality and early mortality.

Results

The study population had a mean age of 69.7 ± 10.1 (19–95) years and a mean logistic EuroSCORE risk of 5.1 ± 5.6 (0.88–73.8). Sedentary patients were significantly older (p = 0.001), obese (p = 0.001), had a higher EuroSCORE risk (p = 0.001), and a higher percentage of complications. Hospital mortality (1.1 % versus 0.4 % (p = 0.014)) and early mortality (1.5 % versus 0.6 % (p = 0.006)) were significantly higher in the sedentary group compared with the active group. However, a sedentary lifestyle was not identified as an independent predictor for hospital mortality (p = 0.61) or early mortality (p = 0.70).

Conclusion

Sedentary patients were older, obese and had a higher EuroSCORE risk. They had significantly more postoperative complications, higher hospital mortality and early mortality. Despite these results, sedentary behaviour could not be identified as an independent predictor for hospital or early mortality.