Matrix Metalloproteinase-9 rs17576 Gene Polymorphism and Behçet’s Disease: Is There an Association?

Background: Clinical studies have reported a significant association between matrix metalloproteinases (MMP), particularly (MMP-9), and inflammatory diseases including Behçet’s disease (BD).

Purpose: To study the relationship between MMP-9 rs17576 gene polymorphism and the development of BD, and its relation to disease activity among Egyptian patients.

Methods: A total of 100 BD patients and 100 healthy control volunteers were genotyped for MMP-9 rs17576 polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), followed by the confirmation of our results in random subgroups using direct DNA sequencing technique.

Results: The frequency of the GG genotype and G allele was significantly higher in BD patients as compared to the normal controls (p = 0.011, OR 8.61; p = 0.03, OR 1.65, respectively). There was no significant association between the MMP-9 rs17576 polymorphism and the clinical outcomes of BD.

Conclusion: our study suggests a significant association of the MMP-9 rs17576 A/G polymorphism with increased risk of BD development in Egyptian patients.     

PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus

Background: PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease.

Objective: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene.

Methods: The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene.

Results: Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs.

Conclusions: The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases.     

Correlation of Proteinuria with Podocyte Foot Process Effacement in IgA Nephropathy: An Ultrastructural Study

Background: Proteinuria is an uncommon clinical manifestation of IgA nephropathy and is usually seen in cases with severe lesions like endocapillary proliferation. However, it is occasionally seen even with cases with mild glomerular manifestations and may even be of nephrotic range.

Predictor: Podocyte foot process effacement.

Outcome: Severity of proteinuria.

Measurements: Podocyte foot process effacement was measured. Morphometric analysis was performed on transmission electron microscope images using a computerized digital photomicrograph system (BioWizard 4.2 Image analysis software, New Delhi, India). Proteinuria was measured quantitatively assigned into five grades.

Results: It was found that as the extent of proteinuria increased, the effacement ratio also increased, and this was most significant between “no” proteinuria and the rest of the categories.

Conclusion: Nephrotic presentation in IgA nephropathy is a known phenomenon and in certain cases may show near normal glomerular morphology with severe foot process effacement on EM being the only significant finding to explain the proteinuria. Proteinuria in these cases shows a significant correlation with degree of foot process effacement. Renal biopsy is important in these cases because they are known to have a better prognosis and are usually steroid responsive.     

Association of LXRα polymorphisms with obesity and obesity-related phenotypes in an Iranian population

Background: Obesity is a multifactorial disorder due to the complex interaction between genetic and environmental factors. Liver X receptor alpha (LXRα), encoded by the gene NR1H3, is involved in lipoprotein metabolism and its genetic variations may also play a role in the aetiology of obesity.

Aim: To assess the association of two NR1H3 polymorphisms (rs11039155 and rs2279238) and their haplotypes with obesity in an Iranian population.

Subjects and methods: A total of 447 unrelated subjects (including 206 overweight, 162 obese and 79 controls) were enrolled in the study and were genotyped by TaqMan assay using DNA from peripheral blood. The association of these two LXRα polymorphisms with the presence of obesity and overweight was assessed.

Results: There was no significant association between the two SNPs and obesity, even after adjustment for age and sex. By logistic regression using a dominant model, the odds ratios for obesity were: 1.32 (0.85–2.74) for rs11039155 and 0.77 (0.30--1.99) for rs2279238. Haplotype analyses identified three common haplotypes GC, GT and AC with frequency greater than 1%, but none of the haplotypes was associated with the risk of obesity.

Conclusions: This study revealed that there was no significant association between LXRα polymorphisms and the presence of obesity in an Iranian population and suggests that these two SNPs are not major contributors to obesity risk in this population.     

Secular trends in cranial morphological traits: a socioeconomic perspective of change and sexual dimorphism in North Americans 1849–1960

Background: The human body has undergone significant changes in stature and other areas, which reflect secular trends associated with socioeconomics.

Aim: To analyse cranial morphological traits for deciphering if they are subject to secular trends.

Subjects and methods: Two documented skeletal collections were sampled for a total of 525 individuals from 1849–1960. Cranial morphological traits were scored and input into time series statistics (logistic regression).

Results: In females, nuchal crests have enlarged, while glabella has decreased. In males, supraorbital margins have dulled, while glabella decreased. Sexual dimorphism increased in supraorbital margins.

Conclusion: The patterns in the data here reflect those found in other areas of the skeleton, namely height, as regards to secular trends. These findings can be extended to stature and cranial changes that parallel socioeconomic trends during the Industrial Revolution, antebellum period and after.     

Pregnane X Receptor Polymorphisms and Risk of Inflammatory Bowel Disease: A Meta-Analysis

Background: Pregnane X receptor (PXR) gene polymorphisms have been widely studied in terms of the association with inflammatory bowel disease (IBD), with inconsistent results.

Objective: The present meta-analysis was performed to assess the association between PXR gene polymorphisms and the susceptibility of IBD, Crohn’s disease (CD), and ulcerative colitis (UC).

Methods: PubMed, Wanfang, and CNKI databases were searched for eligible studies before November 1, 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to calculate the various genetic models using either a fixed-effect or a random-effect model. The heterogeneity of the included studies was examined with Cochran Q and I² statistics. Begg’s rank correlation test and Egger’s linear regression test were used to assess the publication bias.

Results: A total of six studies with 4248 cases and 3853 controls were included in this meta-analysis. Three PXR gene polymorphisms were evaluated: rs1523127, rs2276707, and rs6785049. Our analyses of rs1523127, rs2276707, and rs6785049 suggested that PXR gene polymorphism had no obvious influence on the risk of IBD in Caucasians. Subgroup analyses based on disease type showed similar results.

Conclusion: Our meta-analysis revealed that PXR gene polymorphism may not be significantly associated with IBD susceptibility. However, the number of original studies was limited and further studies with large samples are needed to verify the results.

Abbreviations: PXR = pregnane X receptor, IBD = inflammatory bowel disease, CD = Crohn’s disease, UC = ulcerative colitis, ORs = pooled odds ratios, 95% CIs = 95% confidence intervals, NOS = Newcastle–Ottawa scale, HWE = Hardy–Weinberg equilibrium.     

Lack of Association between MYO9B Gene Polymorphisms and Susceptibility to Coeliac Disease in Caucasians: Evidence from a Meta-Analysis

Objective: Coeliac disease (CD) is a complex disorder influenced by environmental and genetic factors. Recently, a number of studies reported MYO9B gene is associated with CD, but the results are controversial. The aim of this study is to clarify this dispute by means of a meta-analysis.

Methods: The databases of PubMed, Web of Science, and Embase updated to August 2015 were retrieved. Crude odds ratio (OR) and corresponding 95% confidence interval (95%CI) as effect size were calculated by fixed or random effect model according to the heterogeneity.

Results: A total of 8 studies including 2272 cases and 5419 controls were enrolled in this meta-analysis. There was no significant association both in allele and genotype comparisons between the MYO9B (rs2305764, rs2305767, rs1457092) polymorphism and CD in Caucasian populations. No publication bias was detected in this meta-analysis.

Conclusions: This meta-analysis indicates that MYO9B gene polymorphisms might be not associated with CD susceptibility in Caucasians. Further studies are still needed for definitive conclusions.     

Isometric torso muscle endurance profiles in adolescents aged 15–18: normative values for age and gender differences

Objective: The aim of this study was to establish normative values for torso muscle endurance in adolescents aged 15–18 years. It was hypothesized that torso endurance profiles of adolescents differs between males and females and between adolescents and adults.

Background: Decreased torso muscle endurance has been identified as a potential personal risk factor for low back pain development in both adolescents and later years together with being detrimental for athletic performance.

Design: Measurement of torso muscle endurance, established through four tests performed in random order in a healthy adolescent population.

Setting: High school in Novi Sad, Province of Vojvodina, Republic of Serbia.

Methods: Two hundred and ninety-four adolescents from one high school (178 males and 116 females) were grouped into four age strata. Selected isometric torso muscle endurance tests were: Biering-Sørensen test for extensor endurance; Flexor endurance test; right and left Side Bridge tests. The mean, ratio, standard deviation and 25th, 50th and 75th percentile scores were determined for each gender/age strata.

Results and conclusion: Males had higher lateral torso endurance than females. Adolescents in general demonstrate their peak lifetime endurance as they appear more endurable than children and comparable adult groups. These data of endurance times, their ratios and percentiles in healthy normal subjects form a database bridging existing data for children and adults that may be useful for guiding training and rehabilitation.     

Body image,body dissatisfaction and weight status in children from Emilia-Romagna (Italy): comparison between immigrant and native-born

Background: Cross-sectional study among immigrant and native children from Emilia-Romagna (Italy).

Aim: The purpose of the present study was to examine the relative contribution of weight status, ethnicity and sex on body dissatisfaction in a sample of children from Emilia-Romagna (Italy).

Subjects and methods: Primary school children (226 immigrants and 1206 Italians) aged 6–11 years were measured: immigrant children were divided into Asians, Africans, Latin Americans and East Europeans. Height and weight were measured and Body Mass Index (BMI) was calculated. Body image perception was assessed using Body Silhouette Charts. A body dissatisfaction score (BDS) was derived by subtracting the "ideal self" from the "self" score.

Results: Weight status disorders were higher in immigrants than in native-born males; Italian females had higher prevalence of underweight and overweight and lower prevalence of obesity than immigrants peers. BDS rose with the increase of weight status categories.

Conclusions: Awareness of body image size and increasing body dissatisfaction with higher weight status is established in childhood, regardless of ethnicity and gender.     

Modelling foetal growth in a bi-ethnic sample: results from the Born in Bradford (BiB) birth cohort

Background: Attempts to explain the increased risk for metabolic disorders observed in South Asians have focused on the “South Asian” phenotype at birth and subsequent post-natal growth, with little research on pre-natal growth.

Aim: To identify whether divergent growth patterns exist for foetal weight, head (HC) and abdominal circumferences (AC) in a sample of Pakistani and White British foetuses.

Subjects and methods: Models were based on 5553 (weight), 5154 (HC) and 5099 (AC) foetuses from the Born in Bradford birth cohort. Fractional polynomials and mixed effects models were employed to determine growth patterns from ～15 weeks of gestation-birth.

Results: Pakistani foetuses were significantly smaller and lighter as early as 20 weeks. However, there was no ethnic difference in the growth patterns of weight and HC. For AC, Pakistani foetuses displayed a trend for reduced growth in the final trimester.

Conclusion: As the pattern of weight and HC growth was not significantly different during the period under investigation, the mechanism culminating in the reduced Pakistani size at birth may act earlier in gestation. Reduced AC growth in Pakistanis may represent reduced growth of the visceral organs, with consequences for post-natal liver metabolism and renal function.     

Parturition lines in modern human wisdom tooth roots: do they exist,can they be characterized and are they useful for retrospective determination of age at first reproduction and/or inter-birth intervals?

Background: Parturition lines have been described in the teeth of a number of animals, including primates, but never in modern humans. These accentuated lines in dentine are comprised of characteristic dark and light component zones.

Aim: The aim of this study was to review the physiology underlying these lines and to ask if parturition lines exist in the third molar tooth roots of mothers known to have had one or more children during their teenage years.

Methods: Brief retrospective oral medical obstetric histories were taken from four mothers and compared with histological estimates for the timing of accentuated markings visible in longitudinal ground sections of their wisdom teeth.

Results: Evidence of accentuated markings in M3 root dentine matched the age of the mother at the time their first child was born reasonably well. However, the dates calculated for inter-birth intervals did not match well.

Conclusions: Parturition lines corresponding to childbirth during the teenage years can exist in human M3 roots, but may not always do so. Without a written medical history it would not be possible to say with confidence that an accentuated line in M3 root dentine was caused by stress, illness or was a parturition line.     

The role of physical activity,body mass index and maturity status in body-related perceptions and self-esteem of adolescents

Background: Adolescence represents a transitional period which is marked by physical, social and psychological changes. Changes in body shape and physical activity especially alter and shape the psychological well-being of adolescents.

Aim: The purpose of this study was to determine the role of physical activity level, body mass index and maturity status in body-related perception and self-esteem of 11–18 years old adolescents.

Subjects and methods: A total of 1012 adolescents participated in this study. The “Social Physique Anxiety Scale”, “Body Image Satisfaction Scale”, “Physical Self-Perception Profile for Children” and “Rosenberg Self-Esteem Inventory” were administered. Physical activity level and body mass index were assessed using the “Physical Activity Questionnaire” and “Bioelectrical Impedance Analyzer”, respectively.

Results: Regression analysis indicated that body mass index was the only predictor of perceived body attractiveness, social physique anxiety, body image satisfaction and self-esteem for female adolescents. For male adolescents, both physical activity and body mass index were correlated with perceived body attractiveness and social physique anxiety. Pubertal status were not correlated with self-esteem and body-related perceptions for both males and females adolescents.

Conclusion: In summary, body mass index and physical activity plays an important role in body-related perceptions and self-esteem of adolescents.     

Complex role of IL-23R polymorphisms on ankylosing spondylitis: a meta-analysis

Background: The aim of the meta-analysis was to evaluate the association between 10 widely studied polymorphisms of interleukin-23 receptor gene (IL-23R) and ankylosing spondylitis (AS).

Methods: A comprehensive literature search, screening of eligible articles and data extraction was performed independently by two investigators. Further meta-analysis was conducted with STATA 12.0 software (Stata Corp.; College Station, TX, USA). The association between IL-23R polymorphisms and AS was evaluated by odds ratio (OR) and 95% confidence intervals (95% CI).

Results: Twenty-five case–control studies with 8431 cases and 8972 controls were included in this meta-analysis. Quantitative meta-analysis revealed that minor allele frequency (MAF) of rs1004819, rs1495965, and rs2201841 was significantly higher in the AS group (p value < .001, < .001, = .010, respectively). MAF of rs10489629, rs11209026, rs11465804, and rs1343151was significantly lower in the AS group (p value = .002, < .001, = .032, < .001, respectively). However, there is no significant difference between these two groups in rs10889677, rs11209032, and rs7517847 frequency (p value = .128, .237, .131, respectively).

Conclusions: The present study indicates that minor allele carriers of rs1004819, rs1495965, and rs2201841 are susceptible to AS. Conversely, minor alleles of rs10489629, rs11209026, rs11465804, and rs1343151 have protective effect on AS.     

IgA directly inhibits antigen-dependent B cell activation following distinctive distribution of the antigen in mice

Context: Serum IgA suppresses immune responses when exposed to antigens recognized by the antibody; however, the underlying mechanism remains unclear.

Objective: We herein clarified the relationships between changes in antigen distribution and antigen-dependent B cell activation in the presence or absence of IgA against the antigen in mice.

Materials and methods: DBA/1J and HR-1 mice were intravenously injected with ovalbumin (OVA) and anti-OVA monoclonal IgA OA-4. The distribution of the antigen and B cell responses were measured.

Results: B cell activation by injected OVA, namely, increases in anti-OVA IgG production and the populations of B220⁺GL7⁺ and B220⁺CD69^high splenocytes, was diminished by the co-injection of OA-4. Co-injected OA-4 increased OVA in the serum as well as in the bile and gut. This was coincident with its decrease in the urine due to the inhibition of OVA monomer secretion through the formation of immune complexes. The apparent similarities in the association between fluorescein isothiocyanate (FITC)-OVA and splenic B cells in the presence and absence of OA-4 in vivo appeared to be attributed to compensation between the two effects of OA-4; an increase in serum OVA in vivo and inhibition of the association between OVA and B cells, as suggested by in vitro experiments.

Discussion: Based on these results, the stimulation of B cells by OVA may be directly reduced, at least partly, by the neutralization of OVA by OA-4.

Conclusion: IgA may be an effective drug for the treatment of immune disorders due to its ability to blunt antigen-specific B cell activation.     

Geographical and social influences on genetic diversity within the Egyptian population: analyses of Alu insertion polymorphisms

Background: The geographical location of Egypt at the crossroads of several major cultural areas between North Africa and the Middle East has contributed to its population history.

Aim: To analyse the genetic structure of the population living in two geographical parts of Egypt.

Subjects and methods: A sample of 112 Egyptians from the North African part of Egypt (Ismailia sample) and a sample of 52 Egyptians from the Asian part Sinai, have been analysed using 10 Alu insertion polymorphisms.

Results: The results of the present study showed a significant genetic difference between the Sinai and Ismailia samples. The latter showed an evident genetic affinity with North African populations; whereas the Sinai sample was found to be genetically closer to the Middle East populations. The Sinai sample showed a low average heterozygosity, unlike that found in the Ismailia sample.

Conclusion: This study provides new insights into the genetic structure of the Egyptian population living in a land bridge between Africa and Asia. Results suggest a genetic discontinuity between the Sinai population and that of the North African part of Egypt. This discontinuity would have been maintained thanks to geo-climatic and social factors.     

Interferon Regulatory Factor 5 Gene Polymorphisms in Iranian Women with Unexplained Recurrent Pregnancy Loss

Objective: This study aimed to examine the association of three functional IRF5 rs10954213, rs3757385, and rs41298401 polymorphisms with susceptibility to unexplained recurrent pregnancy loss (RPL) among Iranian women from south of Iran.

Methods: 176 women with unexplained RPL and 173 healthy postmenopausal controls were enrolled in this case-control study. Genotyping of the polymorphisms rs10954213 and rs3757385 was carried out using touchdown tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR), and polymorphism rs41298401 was typed using PCR-restriction fragment length polymorphism (PCR-RFLP).

Results: Genotype frequencies were significantly different between RPL cases and controls regarding AG heterozygote genotype of rs10954213, GT genotype of rs3757385, and GG genotype of rs41298401. In addition, allele variants (G for rs10954213, T for rs3757385, and G for rs41298401) showed protective role against RPL, while GG haplotype of two first variants was shown to be a susceptibility factor for the disease.

Conclusion: These data provide the first evidence, to our knowledge, of the protective role of the studied IRF5 gene polymorphisms against unexplained RPL among Iranian women from south of Iran.     

The place of Slovakian paternal diversity in the clinal European landscape

Background: Several demographic events have been postulated to explain the contemporaneous structure of European genetic diversity. First, an initial settlement of the continent by anatomically modern humans; second, the re-settlement of northern latitudes after the Last Glacial Maximum; third, the demic diffusion of Neolithic farmers from the Near East; and, fourth, several historical events such as the Slavic migration.

Aim: The aim of this study was to provide a more integrated picture of male-specific genetic relationships of Slovakia within the broader pan-European genetic landscape.

Subjects and methods: This study analysed a new Y-chromosome data-set (156 individuals) for both SNP and STR polymorphisms in population samples from five different Slovakian localities.

Results: It was found that the male diversity of Slovakia is embedded in the clinal pattern of the major R1a and R1b clades extending over the continent and a similar pattern of population structure is found with Y-specific SNP or STR variation.

Conclusion: The highly significant correlation between the results based on fast evolving STRs on one hand and slow evolving SNPs on the other hand suggests a recent timeframe for the settlement of the area.     

Isotopic and trace element evidence of dietary transitions in early life

Context: Nursing behaviour has significant implications for individual health and population dynamics. Reconstruction of infant and early childhood diet has become a key focus in studies of past populations.

Objective: This paper reviews knowledge about how trace element and stable isotope composition of bone and dental tissues changes during development and how this may influence interpretation of biology and behaviour in past populations.

Methods: Studies of recent populations and osteological samples were reviewed.

Results: Four distinct stages of nutritional intake are recognized: gestation, exclusive breastfeeding, a transitional or weaning stage and fully weaned. The trace element and stable isotope composition of developing foetal and infant tissues differs during each of these stages due to differences in the source of nutrients and changes in metabolic parameters.

Conclusion: Interpretation of early lifetime diet from trace element or stable isotope values requires a comprehensive and validated physiological model for changes during and at the transition between dietary stages. Micro-sampling of dental tissues offers the potential to reconstruct an individual record of early lifetime diet within a chronological framework and has several advantages over traditional cross-sectional techniques. Further research is necessary to understand the factors influencing intra-tooth variability in recovered signals and their chronological interpretation.