ABSTRACT
Aims To investigate whether the FTO rs9939609 A allele (a risk factor for obesity) is associated with measures of alcohol consumption.
Design Population‐based cross‐sectional study and two ...case–control studies.
Setting Poland and the Warsaw area.
Participants A total of 6584 subjects from the WOBASZ survey and two cohorts of alcohol‐dependent patients (n = 145 and n = 148).
Measurements Questionnaire data analysis, rs9939609 typing.
Findings Among individuals drinking alcohol, the obesity‐associated AA genotype was also associated with lower total ethanol consumption sex‐, age‐ and body mass index (BMI)‐adjusted difference: 0.21 g/day, P = 0.012 and distinct drinking habits with relatively low frequency of drinks but larger volume consumed at a time as evidenced by (i) association between AA and frequency/amount of typical drinks (P = 0.023, multiple logistic regression analysis); (ii) inverse correlation between AA and drink frequency adjusted for drink size (P = 0.007 for distilled spirits, P = 0.018 for beer); (iii) decreased frequency of AA odds ratio (OR) = 0.46, P = 0.0004 among those who drank small amounts of distilled spirits (≤100 ml at a time) but frequently (≥1–2 times/week). A decrease of AA was also found in both cohorts of alcohol‐dependent patients versus geographically matched subjects from WOBASZ yielding a pooled estimate of OR = 0.59, confidence interval (CI): 0.40–0.88, P = 0.008. Exploratory analysis showed that those with rs9939609 AA reported lower (by 1.22) mean number of cigarettes/day during a year of most intense smoking (P = 0.003) and were older at start of smoking by 0.44 years (P = 0.016).
Conclusions The FTO AA genotype, independently from its effect on BMI, is associated with measures of ethanol consumption and possibly tobacco smoking.
The etiology of common complex diseases is multifactorial, involving both genetic, and environmental factors. A role for mitochondrial dysfunction and mitochondrial DNA (mtDNA) variation has been ...suggested in the pathogenesis of common complex traits. The aim of this study was to investigate a potential role of mtDNA variants in the development of obesity, diabetes, and atherosclerosis in the Polish population. Whole mtDNA sequences from 415 Polish individuals representing three disease cohorts and a control group were obtained using high-throughput sequencing. Two approaches for the assessment of mtDNA variation were applied, traditional mitochondrial haplogroup association analysis and the mutational or variant load model using the MutPred pathogenicity prediction algorithm for amino acid substitutions in humans. We present a possible association between mildly deleterious mtDNA variant load and atherosclerosis that might be due to having more than one likely mildly deleterious non-synonymous substitution. Moreover, it seems largely dependent upon a few common haplogroup associated variants with MutPred score above 0.5.
Diabetic foot is a diabetes mellitus complication leading to recurrent ulcerations, risk of osteomyelitis and tissue necrosis which may finally result in amputation. Diabetic foot of neuropathic ...origin manifesting as autonomic and sensory motor neuropathy is the most common type of this complication. The aim of this study was to identify risk factors of diabetic foot of neuropathic origin occurrence in patients with type 2 diabetes.
The study included 240 patients, 74 with diabetic foot of neuropathic origin and 166 with diabetes. Cases and controls were matched in terms of age structure. Patients with peripheral arterial disease were excluded from the study. The study was conducted in the Gastroenterology and Metabolic Diseases Department, Medical University of Warsaw, Poland. We used logistic regression models, χ2, U Mann-Whitney's and t-Student tests.
Logistic regression analysis showed that diabetic foot of neuropathic origin risk factors were: male gender (OR = 6.63; 95% CI: 3.31-13.27; p = 0.00001), duration of diabetes (OR = 1.10; 95% CI: 1.06-1.14; p = 0.00001), height (OR = 1.09; 95% CI: 1.06-1.13; p = 0.00001), weight (OR = 1.04; 95% CI: 1.04-1.06; p = 0.00001) and waist circumference (OR = 1.05; 95% CI: 1.02-1.08; p = 0.001). Although there was a correlation between diabetic foot of neuropathic origin and BMI value, it had no impact on DF occurrence risk.
It is possible to identify patients at risk of diabetic foot development by evaluating anthropometric features. The existence of specific factors increasing the odds of diabetic foot of neuropathic origin occurring may lead to the identification of patients at risk of its development.
Homocysteine (Hcy) levels are modulated by nutritional and genetic factors, among which is the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR).
To determine the effects of the MTHTR C677T ...polymorphism, as well as the intake of folate, vitamins B(6) and B(12) on serum Hcy concentration in the Polish population.
Within the framework of the National Multicentre Health Survey (WOBASZ), a representative sample of the whole Polish population aged 20-74 was screened in 2003-2005. Vitamins intake, Hcy level and known MTHTR C677T genotype were available for 1,561 men and 1,712 women.
In the Polish population, T/T, C/T and C/C genotype frequencies were 10%, 43% and 47%, respectively in men, and 9%, 42% and 49%, respectively in women. The T/T genotype was associated with increased levels of Hcy (13.14 μmol/L in men, and 9.77 mmol/L in women) compared to the C/C and C/T genotypes (10.18 and 8.77, respectively), after adjustment for age, methionine, coffee and alcohol intake, smoking and drugs used. In a multivariable linear regression model, among subjects with the T/T genotype, the only factor influencing Hcy was age in women. In the case of the other groups (C/C and C/T), there was a relationship between Hcy and age, alcohol consumption, drugs used, folate and vitamin B(6) in men, and age, smoking, coffee consumption, drugs used, folate and vitamin B(12) in women.
The T/T genotype is associated with higher levels of Hcy (29% in men, and 11% in women) compared to other genotypes. Nutritional factors affect Hcy levels only in the C/C and C/T MTHFR genotypes.
Despite the use of Hymenolepis diminuta as a model organism in experimental parasitology, a full genome description has not yet been published. Here we present a hybrid de novo genome assembly based ...on complementary sequencing technologies and methods. The combination of Illumina paired-end, Illumina mate-pair and Oxford Nanopore Technology reads greatly improved the assembly of the H. diminuta genome. Our results indicate that the hybrid sequencing approach is the method of choice for obtaining high-quality data. The final genome assembly is 177 Mbp with contig N50 size of 75 kbp and a scaffold N50 size of 2.3 Mbp. We obtained one of the most complete cestode genome assemblies and annotated 15,169 potential protein-coding genes. The obtained data may help explain cestode gene function and better clarify the evolution of its gene families, and thus the adaptive features evolved during millennia of co-evolution with their hosts.
Highlights • AA males in general population have lower BDI scores. • Among male suicide victims, AA individuals have higher blood alcohol concentration. • rs53576 has no direct effect either on ...depression or completed suicide.
INTRODUCTION Early detection of diabetic retinopathy (DR) is crucial for preventing irreversible blindness. Recent studies identified some of the genetic factors involved in the pathology of DR, ...although their precise underlying mechanisms remain unclear. OBJECTIVES This pilot study aimed to determine genetic predictors of DR among patients with type 2 diabetes (T2D) and diabetic foot (DF) based on pathogenetic pathways. PATIENTS AND METHODS The study included 114 patients with T2D and DF (64 with DR, 50 without DR). Genetic analysis was performed for each patient and the following alterations were analyzed: rs759853 (AKR1B1), rs1800469 (TGFB1), rs2073618 and rs3134069 (TNFRSF11B), rs6330 and rs11466112 (NGF), rs1801133 (MTHFR), rs8192678 (PPARGC1A), rs1799983 (NOS3), rs1553005 (CALCA), and rs121917832 (CDKN1B). RESULTS Correlations with DR were identified for the following single nucleotide variants (SNVs): rs759853, rs2073618, and rs3134069. Carriers of the G allele of the rs759853 variant had a higher risk of DR in the dominant model (odds ratio OR, 3.0; 95% confidence interval CI, 1.15-7.81; P = 0.02). We analyzed 2 SNVs of the osteoprotegerin gene (rs3134069 and rs2073618), and found that the A allele of the rs3134069 variant decreased the risk of DR in both the recessive and additive models (OR, 3.33; 95% CI, 1.07-10.3; P = 0.04). Conversely, there were fewer carriers of the C allele of the rs2073618 variant in patients with DR in the dominant model (OR, 0.28; 95% CI, 0.09-0.92; P = 0.04). CONCLUSIONS The results of our study suggest that the SNVs rs759853, rs3134069, and rs2073618 may be involved in the development of DR in patients with T2D and DF.
Purpose
Diabetic foot is a complication of long-lasting diabetes mellitus affecting up to 15% of patients, both in type 1 and type 2 diabetes. Osteoprotegerin is involved in osteogenesis and ...calcification. The aim of the study was to assess the role of selected osteoprotegerin gene variants in diabetes patients with diabetic foot.
Methods
The study involved 300 patients with diabetes and diabetic foot and 968 healthy controls. The study group was formed by 243 patients with diabetic foot of neuropathic origin, 102 with diabetic foot of neuroischemic origin and 77 with Charcot neuroarthropathy.
Results
Compared to controls, rs1872426 and rs1485286 showed correlation with diabetic foot in diabetes subjects. Significant associations between rs2073618, rs1872426, rs7464496 and rs1485286 in men were reported. The aforementioned correlations were also present in type 2 diabetes patient subgroup. Variant rs1485286 was associated to diabetic foot of neuropathic origin. Sex-specificity for females was present for rs6993813 in patients with diabetic foot of neuropathic origin and type 1 diabetes. Variants rs1872426, rs2073617 and rs1485286 were correlated with CN. We found that age, body weight, body mass index, waist circumference, hip circumference and waist-hip ratio were among the basic risk factors of diabetic foot.
Conclusions
The following variants
TNFRSF11B
(rs2073618, rs2073617, rs1872426, rs1032128, rs7464496, rs11573829 and rs1485286),
COLEC10
(rs6993813, rs3134069) and
TNFSF11
(rs9533156) present differences in allele frequencies in diabetic foot patients and show correlation with gender, diabetes type and diabetic foot etiology.
INTRODUCTION Diabetic foot (DF) is a serious complication of diabetes mellitus (DM) that occurs due to neuropathy or atherosclerosis of the lower limbs. Omentin (encoded by the ITLN1 gene) has ...been implicated as a protective factor in vascular complications of diabetes, likely due to its endothelial vasodilator activity and its anti‑inflammatory actions. However, susceptibility to DF with respect to the allelic variants of the ITLN1 gene has not been studied so far. OBJECTIVES This study aimed to evaluate the association between the rs2274907 allelic variant of the ITLN1 gene and the occurrence of DF in patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS The study included 670 individuals: 204 with T2DM and DF (DF group), 299 with T2DM without DF (T2DM group), and 167 healthy controls. RESULTS Ischemic heart disease, retinopathy, nephropathy, neuropathy, obesity, hyperlipidemia, and active smoking were more frequent in the DF group than in the T2DM group. Allele A of the rs2274907 variant was observed more frequently in the DF group compared with healthy controls in an additive model (odds ratio OR = 0.7, P = 0.034). This effect was also sex‑specific for males in both the additive and recessive models (OR = 0.6, P = 0.015 and OR = 0.52, P = 0.0017, respectively). However, no differences in the distribution of alleles was observed between the DF and T2DM groups. CONCLUSIONS The rs2274907 variant of the ITLN1 gene is associated with increased prevalence of DF.
Martin-Probst syndrome (MPS) is an X-linked multisystem neurodevelopmental disorder, reported to be caused by the p.D59G mutation in
RAB40AL
. Whereas evidence against the pathogenic role of p.D59G ...has been published, the presence of
RAB40AL
p.D59G continues to be used as a support for MPS diagnosis. Our purpose was to provide further arguments for excluding pathogenicity of
RAB40AL
p.D59G. We detected p.D59G in two healthy males ascertained as family members of p.D59G carriers who underwent whole exome sequencing for diagnostic reasons. Furthermore, we found that p.D59G was present in 2.86 % (4/140) of randomly selected Polish males with higher education.
Conclusion
: Our findings are inconsistent with a causative effect of
RAB40AL
p.D59G on cognitive impairment combined with severe to profound bilateral hearing loss but indicate that p.D59G is a common genetic variation. Our data emphasize the need for genotyping large sample sizes of diverse populations as a basic tool in determining variant pathogenicity.
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