Investigating the role of functional polymorphism of maternal and neonatal vitamin D binding protein in the context of 25‐hydroxyvitamin D cutoffs as determinants of maternal‐neonatal vitamin D status profiles in a sunny mediterranean region

Recent results indicate that dysregulation of vitamin D‐binding protein (VDBP) could be involved in the development of hypovitaminosis D, and it comprises a risk factor for adverse fetal, maternal and neonatal outcomes. Until recently, there was a paucity of results regarding the effect of maternal and neonatal VDBP polymorphisms on vitamin D status during pregnancy in the Mediterranean region, with a high prevalence of hypovitaminosis D. We aimed to evaluate the combined effect of maternal and neonatal VDBP polymorphisms and different maternal and neonatal 25‐hy-droxyvitamin D (25(OH)D) cut‐offs on maternal and neonatal vitamin D profile. Blood samples were obtained from a cohort of 66 mother–child pairs at birth. Our results revealed that: (i) Maternal VDBP polymorphisms do not affect neonatal vitamin D status at birth, in any given internationally adopted maternal or neonatal cut‐off for 25(OH)D concentrations; (ii) neonatal VDBP polymor-phisms are not implicated in the regulation of neonatal vitamin D status at birth; (iii) comparing the distributions of maternal VDBP polymorphisms and maternal 25(OH)D concentrations, with cutoffs at birth, revealed that mothers with a CC genotype for rs2298850 and a CC genotype for rs4588 tended to demonstrate higher 25(OH)D (≥75 nmol/L) during delivery (p = 0.05 and p = 0.04, respec-tively), after adjustments for biofactors that affect vitamin D equilibrium, including UVB, BMI and weeks of gestation. In conclusion, this study from Southern Europe indicates that maternal and neonatal VDBP polymorphisms do not affect neonatal vitamin D status at birth, whereas mothers with CC genotype for rs2298850 and CC genotype for rs4588 demonstrate higher 25(OH)D concen-trations. Future larger studies are required to establish a causative effect of these specific polymor-phisms in the attainment of an adequate (≥75 nmol/L) maternal vitamin D status during pregnancy

Variations in 25-Hydroxyvitamin D in Countries from the Middle East and Europe: the Roles of UVB Exposure and Diet

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Combined effect of age and body mass index on postoperative mortality and morbidity in laparoscopic cholecystectomy patients

BackgroundPrevious studies have assessed the impact of age and body mass index (BMI) on surgery outcomes separately. This retrospective cohort study aimed to investigate the combined effect of age and BMI on postoperative mortality and morbidity in patients undergoing laparoscopic cholecystectomy.MethodsData from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database for laparoscopic cholecystectomy patients between 2008 and 2020 were analyzed. Patient demographics, functional status, admission sources, preoperative risk factors, laboratory data, perioperative variables, and 30-day postoperative outcomes were included in the dataset. Logistic regression was used to determine the association of age, BMI, and age/BMI with mortality and morbidity. Patients were stratified into different subcategories based on their age and BMI, and the age/BMI score was calculated. The chi-square test, independent sample t-test, and ANOVA were used as appropriate for each category.ResultsThe study included 435,052 laparoscopic cholecystectomy patients. Logistic regression analysis revealed that a higher age/BMI score was associated with an increased risk of mortality (adj OR 13.13 95% CI, 9.19–18.77, p < 0.0001) and composite morbidity (adj OR 2.57, 95% CI 2.23–2.95, p < 0.0001).ConclusionOlder age, especially accompanied by a low BMI, appears to increase the post-operative mortality and morbidity risks in laparoscopic cholecystectomy patients, while paradoxically, a higher BMI seems to be protective. Our hypothesis is that a lower BMI, perhaps secondary to malnutrition, can carry a greater risk of surgery complications for the elderly. Age/BMI is strongly and positively associated with mortality and morbidity and could be used as a new scoring system for predicting outcomes in patients undergoing surgery. Nevertheless, laparoscopic cholecystectomy remains a very safe procedure with relatively low complication rates

Vitamin D Receptor Fokl polymorphism is a determinant of both maternal and neonatal Vitamin D concentrations at birth

© 2019 Elsevier Ltd Maternal vitamin D deficiency is considered to be the key determinant of the development of neonatal vitamin D deficiency at birth and during early infancy. Specific vitamin D receptor (VDR) gene polymorphisms have been associated with adverse pregnancy and offspring outcomes. The aim of this study was to evaluate the effect of maternal and neonatal VDR polymorphisms (ApaI, TaqI, BsmI, FokI, Tru9I) on maternal and neonatal vitamin D status. VDR polymorphisms were genotyped in 70 mother-neonate pairs of Greek origin, and classified according to international thresholds for Vitamin D status. Mean neonatal and maternal 25-hydroxy-vitamin D [25(OH)D] concentrations were 35 ± 20 and 47 ± 26 nmol/l, respectively. Neonatal VDR polymorphisms were not associated with neonatal 25(OH)D concentrations. In contrast, mothers with the Fokl FF polymorphism had a 70 % lower risk of vitamin D deficiency [25(OH)D \u3c30 nmol/l] compared with ff ones, after adjustment for several confounders. They were also in 73 % and 88 % lower risk of giving birth to vitamin D deficient [25(OH)D \u3c30 nmol/l] neonates compared with Ff and ff mothers, respectively. These results suggest a protective role of maternal Fokl FF genotype against both maternal and neonatal vitamin D deficiency. Further studies are needed to clarify the complex gene-gene and gene-environment interactions that determine vitamin D status at birth

A study on the association between Angiotensin-I converting enzyme I/D dimorphism and type-2 diabetes mellitus

Type-2 diabetes mellitus (T2DM) is a chronic disorder characterized by a varying range of predominant insulin resistance with relative insulin deficiency, to predominant insulin secretory defect with or without insulin resistance. Familial clustering as well as epidemiological studies has shown that genetic factors play a role in the development and progression of the disease. Among the genetic factors found to be associated with development of T2DM is the angiotensin-I converting enzyme (ACE) gene, which is located on chromosome 17q23. This study was conducted to study the association between ACE gene insertion/deletion (I/D) polymorphism and T2DM in a Lebanese diabetic cohort. Fifty-one patients with T2DM and 40 control subjects from different parts of Lebanon underwent genotyping for the ACE I/D, which was performed by PCR using specific primers. Chi-square and analysis of variance (ANOVA) were used for asso-ciation studies and to assess the differences in the values among the groups. The distribution of the genotypes in the patients was as follows: 15/51 (29.4%) were homozygous for deletion allele (DD genotype), 24/51 (47.1%) were heterozygous (ID genotype), and 12/51 (23.5%) were homo-zygous for insertion allele (II genotype). Among the control subjects, 16/40 (40%) were homo-zygous for deletion (DD genotype), 13/40 (32.5%) were heterozygous (ID genotype), and 11/40 (27.5%) were homozygous for insertion (II genotype). The prevalence of the D-allele in T2DM patients (52.9%) was not significantly different from that in the controls (56.3%). Thus, ACE I/D dimorphism cannot be considered a risk factor for T2DM in the Lebanese population

Association between angiotensin-converting enzyme insertion/deletion gene polymorphism and end-stage renal disease in lebanese patients with diabetic nephropathy

Diabetic nephropathy (DN) is one of the leading causes of end-stage renal disease (ESRD). The development and progression of nephropathy is strongly determined by genetic factors, and few genes have been shown to contribute to DN. An insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE) was reported as a candidate gene predisposing to DN and ESRD. Accordingly, we investigated the frequency of ACE I/D polymorphism in 50 patients with DN, of whom 33 had ESRD and compared them with 64 patients with type 2 diabetes mellitus (T2DM) but with normal renal function. Polymerase chain reaction amplification, using specific primers, was performed to genotype ACE I/D. Chi-square test was used to assess the differences between the groups. The frequencies of the ACE genotypes were as follows: 48% D/D, 40% I/D, and 12% I/I in patients with DN in contrast to 32.8% D/D, 45.3% I/D, and 21.9% I/I in T2DM. The distribution of the D/D, D/I, and I/I genotypes did not significantly differ between T2DM and DN. However, having the D allele carried a risk for the development of DN [odds ratio (OD), 1.71, P = 0.054]. On the other hand, the distribution of the D/D, D/I, and I/I genotypes was significantly different between T2DM and ESRD patients, χ2 = 7.23, P = 0.027. This was reflected by the D allele which carried a risk for the development of ESRD (OR, 2.51, P = 0.0057). These findings suggest that the D allele may be considered as a risk factor for both the development of DN and the progression of DN to ESRD in Lebanese population with T2DM

Vitamin D Related Gene Polymorphisms and Cholesterol Levels in a Mediterranean Population

In addition to its role in bone health, vitamin D (VitD) has been implicated in several pathological conditions. Specifically, VitD deficiency has been linked to an increased risk of dyslipidemia. Atherogenic dyslipidemia is characterized by increased low-density lipoprotein-cholesterol (LDL-C) and decreased high-density lipoprotein-cholesterol (HDL-C). In this study, we examined the association of six single nucleotide polymorphisms (SNPs) in VitD-related genes with VitD and lipid levels, in a cohort of 460 Lebanese participants free from chronic diseases. Our results showed no association of the examined SNPs with VitD concentrations. However, the presence of the minor allele in rs10741657G>A of CYP2R1 was associated with increased levels in LDL-C (β = 4.95, p = 0.04)] and decreased levels in HDL-C (β = −1.76, p = 0.007)]. Interestingly, rs10741657G>A interacted with gender to increase LDL-C levels in females (β = 6.73 and p = 0.03) and decrease HDL-C levels in males HDL-C (β = −1.09, p = 0.009). In conclusion, our results suggest that rs10741657 G>A in CYP2R1 is associated with circulating LDL-C and HDL-C levels in a Lebanese cohort. Although this association was gender-specific, where rs10741657G>A was associated with increased LDL in females and decreased HDL in males, the presence of the minor allele A was associated with increased cardiovascular risk in both genders. These findings need to be validated in a larger population. Further investigations are warranted to elucidate the molecular mechanism of VitD polymorphism and dyslipidemia

Deconvoluting the Biological Roles of Vitamin D-Binding Protein During Pregnancy: A Both Clinical and Theoretical Challenge

The teleological purpose of an ongoing pregnancy is to fulfill its fundamental role of a successful, uncomplicated delivery, in conjunction with an optimal intrauterine environment for the developing fetus. Vitamin D metabolism is adapted to meet both these demands during pregnancy; first by stimulation of calcium absorption for adequate intrauterine bone mineral accrual of the fetus, and second, by enhancing systemic and local maternal tolerance to paternal and fetal alloantigens. Vitamin D-binding protein (VDBP) is one of the key biomolecules that optimize vitamin D homeostasis and also contributes as an immune regulator for a healthy, ongoing pregnancy. In this regard, recent results indicate that dysregulation of VDBP equilibrium could be a risk factor for adverse fetal, maternal, and neonatal outcomes, including preeclampsia, preterm birth, and gestational diabetes. Moreover, it has been hypothesized to be also implicated in the interpretation of vitamin D status in the pregnant state. The aim of this review is to assess available literature regarding the association of VDBP with clinical outcomes during pregnancy, as a potential biomarker for future clinical practice, with a discourse on current knowledge gaps and future research agenda

Study of the association between −403G/A and −28C/G RANTES gene polymorphisms and asthma in Lebanon

Context: Asthma is a complex inflammatory condition often associated with bronchial hyper reactivity and atopy. Genetic and environmental factors are implicated in the etiopathogenesis of asthma. Regulated upon Activation Normal T- cell Expressed and Secreted (RANTES) is a CC chemokine responsible for the recruitment of inflammatory cells, suggesting a possible role for this chemokine in asthma. Both -403A and -28G alleles of the RANTES promoter region were found to be associated with asthma/atopy in some but not all studies. Aim: The purpose of this study was to investigate the genetic influence of -403A and -28G alleles of the RANTES promoter region on the development of asthma in Lebanon. Settings and Design: This case control study was conducted at Makassed Hospital, Beirut on 40 asthmatic patients and 38 healthy controls. Methods: RANTES gene polymorphisms -403G/A and -28C/G alleles were genotyped using PCR-RFLP. Results: No significant differences in allele or genotype frequencies for the RANTES gene polymorphisms between asthmatic patients and controls were found. The difference of the -403 GA genotype frequency between patients and controls was not statisti-cally significant; (OR=0.8, 95% CI=0.2-2.3, P=0.8). Similarly, the difference of the A-allele frequencies between patients and con-trols was not significant (OR=0.824, CI=0.3-2.2, P=0.7). Conclusions: Our data show that RANTES gene promoter polymorphisms are not associated with asthma susceptibility in the Lebanese population