Agnieszka Sobczyk-Kopcioł

Inverse association of the obesity predisposing FTO rs9939609 genotype with alcohol consumption and risk for alcohol dependence

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.

Diabetic foot risk factors in type 2 diabetes patients: a cross-sectional case control study

BackgroundDiabetic foot is a serious condition in patients with a long lasting diabetes mellitus. Diabetic foot treated improperly may lead not only to delayed ulceration healing, generalized inflammation, unnecessary surgical intervention, but also to the lower limb amputation. The aim of this study was to compare diabetic foot risk factors in population with type 2 diabetes and risk factors for diabetes in healthy subjects.MethodsThe study included 900 subjects: 145 with diabetic foot, 293 with type 2 diabetes without diabetic foot and 462 healthy controls matched in terms of mean age, gender structure and cardiovascular diseases absence. Study was conducted in Gastroenterology and Metabolic Diseases Department, Medical University of Warsaw, Poland. In statistical analysis a logistic regression model, U Mann-Whitney’s and t-Student test were used.ResultsThe binomial logit models analysis showed that the risk of diabetic foot in patients with type 2 diabetes was decreased by patient’s age (odds ratio [OR] = 0.94; 95% confidence interval [CI]: 0.92-0.96; p = 0.00001) and hyperlipidaemia (OR = 0.54; 95% CI: 0.36-0.81; p = 0.01). In contrast, male gender (OR = 2.83; 95% CI: 1.86-4.28; p = 0.00001) diabetes duration (OR = 1.04; 95% CI: 1.03-1.06; p = 0.0003), weight (OR = 1.04; 95% CI: 1.03-1.06; p = 0.00001), height (OR = 1.08; 95% CI: 1.05-1.11; p = 0.00001) and waist circumference (OR = 1.028; 95% CI: 1.007-1.050; p = 0.006) increase the risk of diabetic foot. The onset of type 2 diabetes in healthy subjects was increased by weight (OR = 1.035; 95% CI: 1.024-1.046; p = 0.00001), WC (OR = 1.075; 95% CI: 1.055-1.096; p = 00001), hip circumference (OR = 1.03; 95% CI: 1.01-1.05; p = 0.005), overweight defined with body mass index (BMI) above 24,9 kg/m2 (OR = 2.49; 95% CI: 1.77-3.51; p = 0.00001) and hyperlipidaemia (OR = 3.53; 95% CI: 2.57-4.84; p = 0.00001).ConclusionsRisk factors for Type 2 diabetes and diabetic foot are only partially common. Study proved that patients who are prone to developing diabetic foot experience different risk factors than patients who are at risk of diabetes. Identification of relationship between diabetic foot and diabetes risk factors in appropriate groups may help clinicians to focus on certain factors in diabetic foot prevention.

MTHFR 677T Is a Strong Determinant of the Degree of Hearing Loss Among Polish Males with Postlingual Sensorineural Hearing Impairment

Hearing impairment (HI) is the most common sensory handicap. Congenital HI often has a genetic basis, whereas the etiology of nonsyndromic postlingual HI (npHI) usually remains unidentified. Our purpose was to test whether the MTHFR C677T (rs1801133) polymorphism affecting folate metabolism is associated with the occurrence or severity of npHI. We studied rs1801133 genotypes in 647 npHI patients (age <40, sudden sensorineural loss excluded, HI characterized as mean of better ear hearing thresholds for 0.5-8 kHz) and 3273 adult controls from the background population. Genotype distribution among patients and controls was similar, but among male cases (n = 302) we found a dose-dependent correlation of MTHFR 677T with the degree of HI (mean thresholds in dB: 38.8, 44.9, and 53.3, for CC, CT, and TT genotypes, respectively; p = 0.0013, p(cor.) = 0.017). Among male patients rs1801133 TT significantly increased the risk of severe/profound HI (odds ratio = 4.88, p = 0.001). Among controls the known effect of MTHFR 677T on plasma total homocysteine was more pronounced in men than in women (p<0.00004 for genotype-sex interaction) suggesting that in Poland folate deficiency is more prevalent in males. In conclusion, we report a novel strong effect of MTHFR 677T among males with npHI. The functional significance of rs1801133 suggests that these patients may benefit from folate supplementation-an intervention which is simple, cheap, and devoid of side effects.

Risk factors of diabetic foot of neuropathic origin in patients with type 2 diabetes

INTRODUCTION 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. MATERIAL AND METHODS 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-Whitneys and t-Student tests. RESULTS 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. CONCLUSION 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.

No association between MTHFR C677T polymorphism and completed suicide

MTHFR C677T polymorphism (rs1801133) was associated with numerous psychiatric conditions but no prior study investigated whether it predisposes to completed suicide. We typed rs1801133 in 692 suicide victims and 3257 controls representative of a Polish adult population (the WOBASZ cohort). Although we had a power of 0.8 to detect (at alpha 0.05) an allelic OR=1.19, we did not find significant difference among suicides vs. controls in the prevalence of the MTHFR 677T allele (OR=1.02, p=0.759) or the TT genotype (OR=1.01, p=0.926). Since among controls we found an association between TT and depression defined by Beck Depression Inventory (BDI, OR=1.61, p=0.049) we also compared suicides with controls without signs of depression (BDI ≤ 11) but found no association (OR=1.0, p=0.976). Analyses within suicides showed trends (not significant after Bonferroni correction) for correlations between the dose of the T allele and age at death among males and blood ethanol concentration among females, who committed suicide under the influence of alcohol. We conclude that MTHFR C677T polymorphism is not a risk factor for completed suicide. The sex-specific trends for correlations between rs1801133 and age at death, and blood ethanol concentration should be studied further.

Risk factors of charcot neuroarthropathy development in patients with type 2 diabetes.

AIM Charcot neuroarthropathy is a very rare form of diabetic foot syndrome occurring among others in patients with diabetes mellitus. Charcot neuroarthropathy leads to bone tissue destruction and may result in foot amputation. The aim of the study was to identify risk factors of Charcot neuroarthropathy occurrence in patients with diabetic foot and type 2 diabetes. MATERIALS The study included 144 patients with type 2 diabetes; 33 with Charcot neuroarthropathy and 111 with diabetic foot of neuropathic origin without neuroarthropathy. The study was perform in Gastroenterology and Metabolic Diseases Department, Medical University of Warsaw, Poland. RESULTS The regression analysis showed that Charcot neuroarthropathy occurrence risk factors were: male gender (OR=4.94, 95% CI:1.63-15.03, p=0.003), age (OR=0.92, 95% CI:0.87-0.96, p=0.0001), diabetic foot duration (OR=1.19, 95% CI:1.08-1.32, p=0.00002) and height (OR=1.078, 95% CI:1.019-1.140, p=0.007). A positive effect on Charcot neuroarthropathy presence was exerted by body weight (OR=1.027, 95% CI:1.003-1.051, p=0.03) and hips circumference (OR=1.034, 95% CI:0.997-1.072, p=0.04). CONCLUSIONS The existence of the specific factors influencing Charcot neuroarthropathy development may result in earlier identification of patients at risk of its development. There is a necessity to take special care for patients prone to develop Charcot neuroarthropathy in order to prevent its occurrence and severe complications.

OXTR polymorphism in depression and completed suicide—A study on a large population sample

In the light of contradictory results concerning OXTR polymorphism rs53576 and depression, we decided to verify the potential association between the two on 1) a large, ethnically homogenous sample of 1185 individuals who completed the Beck Depression Inventory (BDI), as well as on 2) a sample of 763 suicide victims. In the population sample, AA males showed significantly lower BDI scores (p=0.005, pcor=0.030). Exploratory analyses suggested that this effect was limited to a subgroup within 0-9 BDI score range (p=0.0007, U-Mann Whitney test), whereas no main effect on depressive symptoms (BDI>9) was found. In the suicide sample no association with rs53576 genotype was present. Exploratory analyses in suicides revealed higher blood alcohol concentration (BAC) among AA than GG/GA males (p=0.014, U-Mann Whitney test). Our results show that the OXTR rs53576 variant modulates the mood in male individuals and may positively correlate with alcohol intake among male suicides, but is not associated with suicide or depression. The study adds to the growing knowledge on rs53576 genotype characteristics.