Association of ACE I/D polymorphism with obstructive sleep apnea susceptibility: evidence based on 2,228 subjects

Background

Whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene increases susceptibility to obstructive sleep apnea (OSA) is controversial and still undetermined. Therefore, this meta-analysis was performed to systematically assess the possible association between them.

Methods

The OVID, Medline, Embase, Web of Science, CNKI, and Wangfang databases were searched to identify eligible studies focusing on the association between ACE polymorphism I/D and susceptibility to OSA.

Results

A total of 2,228 subjects from nine studies were subjected to meta-analysis. Overall, ACE polymorphism I/D had no statistically significant association with increased OSA risk under all genetic models (P?>?0.05). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all genetic models (P?>?0.05). However, ACE polymorphism I/D was significantly associated with susceptibility to OSA with hypertension in Asians under heterozygous comparison and dominant model. The ID genotype carriers and D allele carriers (ID + DD) were about 53 % less likely (odds ratio (OR)?=?0.47, 95 % confidence interval (CI)?=?0.29–0.74; P?=?0.001) and about 52 % less likely (OR?=?0.48, 95 % CI?=?0.24–0.99; P?=?0.047), respectively, to have OSA with hypertension compared to carriers of the II genotype.

Conclusions

ACE polymorphism I/D had no statistically significant association with increased OSA risk, but the II genotype of ACE may be a risk factor for OSA with hypertension in Asians. OSA cases who develop hypertension may derive from a different mechanism compared to essential hypertension. Studies with large sample size and representative population are warranted to verify this finding.     

Prevalence of irritable bowel syndrome and functional dyspepsia,overlapping symptoms,and associated factors in a general population of Bangladesh

Background

This community-based survey aimed to find out the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), overlapping symptoms, and associated factors for overlap.

Method

By cluster sampling method, 3,000 (1,523 male) randomly selected adult subjects in the Sylhet district of Bangladesh were interviewed by a questionnaire based on ROME III criteria. Multivariate logistic regression analyses were done to find out the factors for overlap with significance level set at ≤0.05.

Results

The mean age of the study population was 33.9?±?16.4 years. Prevalence of IBS and FD and IBS-FD were 12.9 % (n?=?387), 8.3 % (n?=?249), and 3.5 % (n?=?105), respectively. Approximately 27.1 % of IBS patients and 42.1 % of FD patients had overlapping IBS-FD. The odds ratio for IBS-FD overlap was 6.3 (95 % CI, 4.8–8.4). Mean age (p?=?0.011) and epigastric pain (p?=?0.002) were more in overlap patients than FD alone, whereas epigastric pain syndrome subtype (p?<?0.009) was more prevalent in lone FD subjects. In the multivariate logistic analysis, early satiety (OR, 3.0; 95 % CI, 1.2–7.5; p?=?0.018) and epigastric pain (OR, 14.5; 95 % CI, 5.0–42.1; p?=?0.000) in FD patients appeared as independent risk factors for overlap. Bloating (p?=?0.026), <3 stools per week (p?=?0.050), abdominal pain reduced by defecation (p?=?0.002), abdominal pain severity score (p?=?0.004), and overall symptom frequency score (p?=?0.000) were more in overlap patients than IBS-alone patients. In IBS patients, bloating (OR, 3.6; CI, 2.0–6.5; p?=?0.000) was found as potential symptom associated with IBS-FD overlap.

Conclusion

FD was a less prevalent disorder than IBS in our community, and significant overlap existed between the two disorders. Early satiety, epigastric pain, and bloating were important factors associated with overlap.     

Effects of obstructive sleep apnea severity on serum lipid levels in Greek children with snoring

Background

Although obstructive sleep apnea (OSA) is related to dyslipidemia in adults, limited data are available regarding its effects on serum lipids during childhood. Aim of this study was to assess the potential relationships between severity of OSA and cholesterol or triglyceride levels in a cohort of Greek children.

Methods

Data from children with snoring who underwent polysomnography and complete serum lipids measurements during a specified study period were analyzed retrospectively.

Results

Overall, obese children (n?=?261) had lower HDL cholesterol levels than non-obese subjects (n?=?113) (49.6?±?10.5 vs. 53.9?±?11.4 mg/dL; p?=?0.001) and higher triglyceride concentrations (69.8?±?32.2 vs. 63.2?±?27 mg/dL; p?=?0.041). Non-obese subjects with moderate-to-severe OSA did not differ in triglycerides, total, and LDL cholesterol concentrations but had lower HDL cholesterol, when compared to non-obese children with primary snoring/mild OSA (50.4?±?13.1 vs. 54.9?±?10.7 mg/dL; p?=?0.008). The risk for having low HDL cholesterol (??40 mg/dL) was threefold higher in non-obese subjects with moderate-to-severe OSA than in those with primary snoring/mild OSA, even after adjustment for age and gender [OR?=?3.44 (95% CI 1.44 to 8.24; p?=?0.006)]. Concentrations of serum lipids in obese children were not associated with severity of OSA. HDL cholesterol was 48.5?±?8.7 mg/dL in subjects with moderate-to-severe OSA and 50.0?±?11.1 mg/dL in children with primary snoring/mild OSA (p?=?0.519).

Conclusions

HDL cholesterol levels are inversely related to severity of OSA in non-obese children with snoring.     

Single-incision laparoscopic colectomy versus conventional multiport laparoscopic colectomy: a meta-analysis of comparative studies

Objective

This study aimed to compare single-incision laparoscopic colectomy (SILC) to conventional multiport laparoscopic colectomy (MLC).

Background

Single-incision laparoscopic surgery (SILS) is a minimally invasive technique being recently applied to colorectal surgery. A number of studies comparing SILC to conventional MLC have recently been published.

Methods

A literature search of PubMed and MEDLINE databases for studies comparing SILC to conventional MLC was conducted. The primary outcome measures for meta-analysis were postoperative complications, length of stay, and operative time. Secondary outcome measures were incision length, estimated blood loss, and number of lymph nodes harvested.

Results

Fifteen studies comparing 467 patients undergoing SILC to 539 patients undergoing conventional MLC were reviewed and the data pooled for analysis. Patients undergoing SILC had a shorter length of stay (pooled weighted mean difference (WMD)?=??0.68; 95 % CI?=??1.20 to ?0.16; p?=?0.0099), shorter incision length (pooled WMD?=??1.37; 95 % CI?=??2.74 to 0.000199; p?=?0.05), less estimated blood loss (pooled WMD?=??20.25; 95 % CI?=??39.25 to ?1.24; p?=?0.037), and more lymph nodes harvested (pooled WMD?=?1.75; 95 % CI?=?0.12 to 3.38; p?=?0.035), while there was no significant difference in the number of postoperative complications (pooled odds ratio?=?0.83; 95 % CI?=?0.57 to 1.20; p?=?0.33) or operative time (pooled WMD?=?5.06; 95 % CI?=??2.91 to 13.03; p?=?0.21).

Conclusion

SILC appears to have comparable results to conventional MLC in the hands of experienced surgeons. Prospective randomized trials are necessary to define the relative benefits of one procedure over the other.     

Obstructive sleep apnea and acute myocardial infarction severity: ischemic preconditioning?

Background

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia (IH). In animal models, IH has been shown to protect the myocardium during periods of ischemia by reducing infarct size. However, this phenomenon of “ischemic preconditioning” has not been investigated among OSA patients with acute myocardial infarction (MI). This study investigates the role of OSA on MI severity as measured by cardiac enzymes, specifically troponin-T, among patients with an acute MI.

Methods

This is an observational cohort study of patients ≥18 years of age who were hospitalized with an acute MI. Each participant underwent portable sleep monitoring (Apnea Link Plus); OSA was defined as an apnea–hypopnea index ≥5/h. Multivariable regression analysis was conducted to assess the relationship between OSA and highly sensitive troponin-T levels.

Results

In our entire cohort of acute MI patients (n?=?136), 77 % of the sample had evidence of sleep disordered breathing, with 35 % of the sample having OSA (i.e., an AHI >5). Higher AHI was associated with lower peak troponin-T levels in partially adjusted models (β?=??0.0320, p?=?0.0074, adjusted for age, gender, and race) and fully adjusted models (β?=??0.0322, p?=?0.0085) (additionally adjusted for smoking, hypertension, hyperlipidemia, body mass index, history of prior cardiovascular or cerebrovascular disease, diabetes and baseline admission creatinine levels). The mean value of the log-transformed peak troponin-T variable was used to dichotomize the outcome variable. In both partially (OR 0.949, CI 0.905–0.995, p?=?0.03) and fully adjusted (OR 0.918, CI 0.856–0.984, p?=?0.0151) logistic regression models, the OR for AHI suggests a protective effect on high troponin-T level.

Conclusions

Our study demonstrates that patients with OSA have less severe cardiac injury during an acute non-fatal MI when compared to patients without OSA. This may suggest a cardioprotective role of sleep apnea during acute MI via ischemic preconditioning.     

Preoperative adipocytokines as a predictor of surgical infection after colorectal surgery: a prospective survey

Background

Infections are the leading cause of morbidity and mortality after colorectal surgery. Obesity is a well-known risk factor for wound infection, but it does not seem to increase the risk of other infectious complications. The aim of this study was to look for a relationship between the fatty tissue metabolism measured by adipocytokine levels and the risk of postoperative infection.

Patients and methods

Preoperative plasma levels of eight adipocytokines, cholesterol, triglycerides, insulin and C-reactive protein (CRP) were measured in consecutive patients undergoing elective colorectal surgery between June 2008 and June 2011. Information about epidemiological and clinical characteristics was obtained for each patient. All infections in the 30 days following surgery were recorded.

Results

Among the 174 patients included, 49 (28 %) presented with a postoperative infection: 41 surgical site infections and 8 other infections. Preoperative leptin, insulin and CRP were significantly higher in patients with postoperative infection (p?=?0.025, p?=?0.020 and p?=?0.044, respectively), but only leptin was predictive of infection in multivariate analysis (odds ratio (OR)?=?1.89, 95 % confidence interval (CI) 1.18–3.03, p?=?0.008). The predictive value of leptin was slightly lower for surgical site infection (OR?=?1.65, 95 % CI 1.06–2.55, p?=?0.025). Leptin levels were independent of the other adipocytokine levels but not of the body mass index.

Conclusion

Although markers of inflammation and insulin resistance are also related to the onset of surgical infection, leptin correlates more closely with the risk of infection than does any other factor. However, its effect could be partially mediated by the body mass index.     

Sleep-disordered breathing and daytime napping are associated with maternal hyperglycemia

Objectives

Sleep disturbances in pregnancy may impair glucose mechanism. This study aimed to examine associations of sleep-disordered breathing, sleep, and nap duration with 1-h glucose challenge test (GCT) levels in pregnant women after controlling for known risk factors for gestational diabetes.

Methods

This is a case–control study of 104 pregnant women. All women underwent full polysomnography and a GCT and completed the multivariable apnea prediction and Pittsburgh Sleep Quality indexes. The primary outcome was maternal hyperglycemia measured by GCT. Bivariate and multivariable logistic regression analyses were performed.

Results

Over 13 % subjects reported habitual snoring in the first trimester. Only 9.3 % women with normoglycemia (GCT?<?135) were habitual snorers, whereas 45.5 % women with hyperglycemia (GCT?≥?135) had habitual snoring (p?<?0.001). Sleep-disordered breathing symptoms (loud snoring, snorting/gasping, and apneas) (odds ratio (OR) 2.85; 95 % confidence interval (CI) 1.50–5.41; p?=?0.001) and total nap duration (OR 1.48; 95 % CI 0.96–2.28; p?=?0.08) were associated with hyperglycemia. After adjusting for confounders, sleep-disordered breathing symptoms (OR 3.37; 95 % CI 1.44–8.32; p?=?0.005) and nap duration (OR 1.64; 95 % CI 1.00–2.681.02; p?=?0.05) continued to be associated with hyperglycemia. However, the primary exposure measure, the apnea/hypopnea index in the first trimester was not significantly associated with hyperglycemia (OR 1.03; 95 % CI 0.83–1.28; p?=?0.77).

Conclusions

Sleep-disordered breathing symptoms and nap duration are associated with hyperglycemia. Sleep duration was not associated with hyperglycemia. Research is needed concerning whether women with sleep-disordered breathing and/or daytime napping are at risk for gestational diabetes.     

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data

Aims/hypothesis

We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes.

Methods

Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies.

Results

Data were available for 29 predominantly European studies (five cohort, 24 case–control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01–1.11]; p?=?0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04–1.19]; p?=?0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00–1.06]; p?=?0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings.

Conclusions/interpretation

Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.     

Predictive value of total atrial conduction time measured with tissue Doppler imaging for postoperative atrial fibrillation after coronary artery bypass surgery

Objective

Postoperative atrial fibrillation (POAF) complicating coronary artery bypass grafting surgery (CABG) increases morbidity and stroke risk. Total atrial conduction time (PA-TDI duration) has been identified as an independent predictor of new-onset atrial fibrillation (AF). We aimed to assess whether PA-TDI duration is a predictor of AF after CABG.

Methods

In 128 patients who had undergone CABG, preoperative clinical and echocardiographic data were compared between patients with and without POAF. The PA-TDI duration was assessed by measuring the time interval between the beginning of the P wave on the surface ECG and point of the peak A wave on TDI from left atrium (LA) lateral wall just over the mitral annulus.

Results

Patients with POAF (38/128, 29.6 %) were older (68.1?±?11.1 vs. 59.3?±?10.2 years; p?<?0.001), had higher LA maximum volume, had prolonged PA-TDI duration, and had lower ejection fraction compared with patients without POAF. PA-TDI duration was found to be significantly increased in POAF group (134.3?±?19.7 vs. 112.5?±?17.7 ms; p?=?0.01). On multivariate analysis, age (95 % CI?=?1.03–1.09; p?=?0.003), LA maximum volume (95 % CI?=?1.01–1.06; p?=?0.03), and prolonged PA-TDI duration (95 % CI, 1.02–1.05; p?=?0.001) were found to be the independent risk factors of POAF.

Conclusions

In this study, LA maximum volume and PA-TDI duration were found to be the independent predictors of the development of POAF after CABG. Echocardiographic predictors of left atrial electromechanical dysfunction may be useful in risk stratifying of patients in terms of POAF development after CABG.     

PTSD Risk and Mental Health Care Engagement in a Multi-War Era Community Sample of Women Veterans

BACKGROUND

Post-traumatic stress disorder (PTSD) is common in women veterans (WVs), and associated with significant co-morbidity. Effective treatment is available; however, PTSD is often unrecognized.

OBJECTIVES

Identify PTSD prevalence and mental healthcare (MHC) use in a representative national WV sample.

DESIGN AND PARTICIPANTS

Cross-sectional, population-based 2008–2009 national survey of 3,611 WVs, weighted to the population.

MAIN MEASURES

We screened for PTSD using a validated instrument, and also assessed demographic characteristics, health characteristics, and MHC use in the prior 12 months. Among those screening positive, we conducted multivariate logistic regression to identify independent predictors of MHC use.

KEY RESULTS

Overall, 13.0 % (95 % confidence interval [CI] 9.8–16.2) of WVs screened PTSD-positive. Veterans Health Administration (VA) healthcare was used by 31.1 % of PTSD-positives and 11.4 % of PTSD-negatives (p?<?0.001). Among those screening positive, 48.7 % (95 % CI 35.9–61.6) used MHC services (66.3 % of VA-users, 40.8 % of VA-nonusers; p?<?0.001). Having a diagnosis of depression (OR?=?8.6; 95 % CI 1.5–48.9) and VA healthcare use (OR?=?2.7; 95 % CI 1.1–7.0) predicted MHC use, whereas lacking a regular provider for health care (OR?=?0.2; 95 % CI 0.1–0.4) and household income below the federal poverty level (OR?=?0.2; 95 % CI 0.1–0.5) predicted nonuse.

CONCLUSIONS

More than one in eight WVs screened positive for PTSD. Though a majority of VA-users received MHC, low income predicted nonuse. Only a minority of VA-nonusers received MHC. The majority of WVs use non-VA healthcare providers, who may be unaware of their veteran status and PTSD risk. VA outreach to educate VA-nonusers and their healthcare providers about WVs’ PTSD risk and available evidence-based VA treatment options is one approach to extend the reach of VA MHC. Research to characterize barriers to VA MHC use for VA-nonusers and low income VA-users is warranted to better understand low service utilization, and to inform program development to engage more WVs in needed MHC.     

PTGER4 modulating variants in Crohn’s disease

Purpose

Variants modulating expression of the prostaglandin receptor 4 (PTGER4) have been reported to be associated with Cohn’s disease (CD), but the clinical impact remains to be elucidated. We analyzed these variants in a large German inflammatory bowel disease (IBD) cohort and searched for a potential phenotype association.

Methods

The variants rs4495224 and rs7720838 were studied in adult German IBD patients (CD, n?=?475; ulcerative colitis (UC), n?=?293) and healthy controls (HC, n?=?467). Data were correlated to results from NOD2 genotyping and to clinical characteristics.

Results

We found a significant association for the rs7720838 variant with overrepresentation of the T allele to CD (p?=?0.0058; OR 0.7703, 95 % CI 0.641–0.926) but not to UC. Furthermore, logistic regression analysis revealed that the presence of the T allele was associated with stricturing disease behavior in CD patients (p?=?0.03; OR 1.84, 95 % CI 1.07–3.16). Interestingly, the chance for developing stricturing disease behavior was enhanced if mutant alleles in both rs7720838 and NOD2 were present (OR 2.87, 95 % CI 1.42–5.81; p?=?0.003). No overall association to CD or UC was found for the rs4495224 variant.

Conclusions

The PTGER4 modulating variant rs7720838 increases susceptibility for CD and might resemble a risk factor for stricturing disease behavior.     

Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus

Angiotensin II, the major effective molecule of the renin-angiotensin system, plays a vital role in the development of systemic lupus erythematosus (SLE). To study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in Egyptian children with SLE and its correlation with serum ACE level and SLE manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE in comparison to 100 healthy controls using polymerase chain reaction-based restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) to confirm the results of the genotyping. Serum ACE level measurement was done using ELISA technique. The frequencies of C-containing genotypes (AC?+?CC) and C-allele of AT1R (A1166C) were significantly higher in SLE patients compared to controls (p?<?0.0001, OR?=?4.9, 95% CI?=?2.7–8.8; p ? 0.0001, OR?=?3.6, 95% CI?=?2.2–5.9, respectively). Lupus nephritis (LN) patients had significantly higher frequency of (AC?+?CC) genotypes and C-allele compared with controls (p ? 0.0001, OR?=?5.1, 95% CI?=?2.7–9.7; p ? 0.0001, OR?=?3.5, 95% CI?=?2.1–6.02, respectively). Mean serum ACE levels were significantly higher in SLE patients compared to controls (p ? 0.0001). There were no associations between AT1R gene polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R gene polymorphism can be considered a risk factor for the development of SLE in Egyptian children.     

An electrocardiogram-based analysis evaluating sleep quality in patients with obstructive sleep apnea

Objective

The study compares polysomnography (PSG) and cardiopulmonary coupling (CPC) sleep quality variables in patients with (1) obstructive sleep apnea (OSA) and (2) successful and unsuccessful continuous positive airway pressure (CPAP) response.

Patients/methods

PSGs from 50 subjects (32 F/18 M; mean age 48.4?±?12.29 years; BMI 34.28?±?9.33) were evaluated. OSA patients were grouped by no (n?=?16), mild (n?=?13), and moderate to severe (n?=?20) OSA (apnea–hypopnea index (AHI)?≤?5, >5–15, >15 events/h, respectively). Outcome sleep quality variables were sleep stages in non-rapid eye movement, rapid eye movement sleep, and high (HFC), low (LFC), very low-frequency coupling (VLFC), and elevated LFC broad band (e-LFC_BB). An AHI?≤?5 events/h and HFC?≥?50 % indicated a successful CPAP response. CPC analysis extracts heart rate variability and QRS amplitude change that corresponds to respiration. CPC-generated spectrograms represent sleep dynamics from calculated coherence product and cross-power of both time series datasets.

Results

T tests differentiated no and moderate to severe OSA groups by REM % (p?=?0.003), HFC (p?=?0.007), VLFC (p?=?0.007), and LFC/HFC ratio (p?=?0.038) variables. The successful CPAP therapy group (n?=?16) had more HFC (p?=?0.003), less LFC (p?=?0.003), and e-LFC_BB (p?=?0.029) compared to the unsuccessful CPAP therapy group (n?=?8). PSG sleep quality measures, except the higher arousal index (p?=?0.038) in the unsuccessful CPAP group, did not differ between the successful and unsuccessful CPAP groups. HFC?≥?50 % showed high sensitivity (77.8 %) and specificity (88.9 %) in identifying successful CPAP therapy.

Conclusions

PSG and CPC measures differentiated no from moderate to severe OSA groups and HFC?≥?50 % discriminated successful from unsuccessful CPAP therapy. The HFC?≥?50 % cutoff showed clinical value in identifying sleep quality disturbance among CPAP users.     

Impact of continuous positive airway pressure on C-reactive protein in patients with obstructive sleep apnea: a meta-analysis

Purpose

C-reactive protein (CRP) is associated with the development of obstructive sleep apnea (OSA) and cardiovascular diseases. Continuous positive airway pressure (CPAP) is an effective treatment for OSA, but the impact of CPAP therapy on CRP levels in patients with OSA remains unclear. To obtain this information, we performed a meta-analysis to determine whether effective CPAP therapy could reduce serum CRP levels.

Methods

A comprehensive literature search was performed to identify studies that examined the impact of CPAP on serum CRP levels in OSA patients who were treated with CPAP for at least 4 weeks. Standardized mean difference (SMD) was used to analyze the summary estimates for CPAP therapy.

Results

Fourteen self-control design studies involving 1199 patients with OSA met the inclusion criteria. Meta-analysis indicated that the overall SMD for the CRP levels was 0.64 units (95 % confidence interval (CI) 0.40 to 0.88) before and after CPAP therapy; test for overall effect z?=?5.27 (P?=?0.000). Subgroup analysis showed that evolution of CRP decreased non-significantly in less than 3 months (SMD, 0.26, 95 % CI ?0.08 to 0.60, P?=?0.138), significantly decreased after 3 months (SMD, 0.68, 95 % CI 0.34 to 1.02, P?=?0.000), and further declined after 6 months (SMD, 0.74, 95 % CI 0.43 to 1.05, P?=?0.000).

Conclusions

The systemic inflammation, as measured by CRP, was present and significantly reduced by effective CPAP therapy in patients with OSA. The use of CRP levels may be clinically recognized as a valuable predictor for OSA treatment monitoring.     

XPD Asp312Asn polymorphism is a risk factor for prostate cancer

Purpose

The association between Asp312Asn and Lys751Gln polymorphisms of Xeroderma pigmentosum Group D (XPD) and prostate cancer risk are still inconclusive. For better understanding of the effects of these two polymorphisms on prostate cancer risk, a meta-analysis was performed.

Methods

An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and prostate cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI).

Results

A total of seven case–control studies were identified, among which five studies (1,257 cases and 1,956 controls) were eligible for Asp312Asn polymorphism and six studies (1,451 cases and 2,375 controls) were eligible for Lys751Gln polymorphism. Asp312Asn polymorphism was associated with an increased risk of prostate cancer in additive and recessive genetic models (additive model: OR?=?1.68, 95?% CI?=?1.28–2.22, P?=?0.00; recessive model: OR?=?1.65, 95?% CI?=?1.27–2.15, P?=?0.00). In the subgroup analysis, Asp312Asn polymorphism was associated with an increased risk of prostate cancer among Asians in all three genetic models (additive model: OR?=?2.09, 95?% CI?=?1.39–3.14, P?=?0.00; dominant model: OR?=?1.49, 95?% CI?=?1.12–1.98, P?=?0.01; recessive model: OR?=?1.93, 95?% CI?=?1.31–2.83, P?=?0.00). However, no significant associations were found between Lys751Gln polymorphism and prostate cancer risk in the overall analyses or the subgroup analyses by ethnicity.

Conclusions

The results of this meta-analysis indicate that the XPD Asp312Asn polymorphism is a risk factor for prostate cancer development.     

Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women

Background/Aims

Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women.

Methods

We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women’s Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry.

Results

Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38–0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36–0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07–0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09–0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57–1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56–3.8, p = 0.45) women.

Conclusions

African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.     

Association of 24 bp Duplication of Human CHIT1 Gene with Asthma in a Heterozygous Population of North India: A Case–Control Study

Purpose

CHIT1 is expressed by pulmonary macrophages, which is typically the site of entry for many environmental fungi that may increase the risk of pulmonary fungal infection and lead to hypersensitivity. The conserved expression of this gene in humans suggests its physiological importance in the mammalian lung.

Methods

The present study was conducted with a total of 964 subjects, including 483 healthy controls and 481 asthma patients. DNA samples were extracted from blood, and the genotyping was done using polymerase chain reaction method.

Results

Statistical analysis revealed that the 24 bp duplication in CHIT1 gene polymorphism shows highly significant association in heterozygous (wild/dup) genotype with OR 1.74, 95 % CI (1.29–2.36), and p = 0.000. However, the homozygous mutant genotype (dup/dup) was found to be non-significant with OR 1.06, 95 % CI (0.69–1.63), and p = 0.786. The combination of both wild/dup and dup/dup was also found to be highly significant with OR 1.57, 95 % CI (1.18–2.11), and p = 0.002.

Conclusions

This is the first study conducted in India which reports a significant association between 24 bp duplication in CHIT1 gene polymorphism and asthma in the studied North Indian population.     

A variant in the G6PC2/ABCB11 locus is associated with increased fasting plasma glucose, increased basal hepatic glucose production and increased insulin release after oral and intravenous glucose loads

Aims/hypothesis

An association between elevated fasting plasma glucose and the common rs560887 G allele in the G6PC2/ABCB11 locus has been reported. In Danes we aimed to examine rs560887 in relation to plasma glucose and serum insulin responses following oral and i.v. glucose loads and in relation to hepatic glucose production during a hyperinsulinaemic–euglycaemic clamp. Furthermore, we examined rs560887 for association with impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT), type 2 diabetes and components of the metabolic syndrome.

Methods

rs560887 was genotyped in the Inter99 cohort (n?=?5,899), in 366 young, healthy Danes, in non-diabetic relatives of type 2 diabetic patients (n?=?196), and in young and elderly twins (n?=?159). Participants underwent an OGTT, an IVGTT or a 2 h hyperinsulinaemic–euglycaemic clamp.

Results

The rs560887 G allele associated with elevated fasting plasma glucose (p?=?2?×?10^?14) but not with plasma glucose levels at 30 min (p?=?0.9) or 120 min (p?=?0.9) during an OGTT. G allele carriers had elevated levels of serum insulin at 30 min during an OGTT (p?=?1?×?10^?4) and relatives of type 2 diabetes patients carrying the G allele had an increased acute insulin response (p?=?4?×?10^?4) during an IVGTT. Among elderly twins, G allele carriers had higher basal hepatic glucose production (p?=?0.04). Finally, the G allele associated with the risk of having IFG (OR 1.26, 95% CI 1.08–1.47, p?=?0.002), but not with IGT (OR 0.94, 95% CI 0.82–1.08, p?=?0.4) or type 2 diabetes (OR 0.93, 95% CI 0.84–1.04, p?=?0.2).

Conclusions/interpretation

The common rs560887 G allele in the G6PC2/ABCB11 locus is associated with increased fasting glycaemia and increased risk of IFG, associations that may be partly related to an increased basal hepatic glucose production rate.     

Sleep duration and body mass index in children and adolescents with and without obstructive sleep apnea

Purpose

The prevalence of pediatric obesity and short sleep duration has simultaneously increased in recent decades. Sleep plays a critical role in metabolic and endocrine regulation and insufficient sleep has been shown to be associated with changes in metabolism. Obesity, a major risk factor for obstructive sleep apnea (OSA), has been also associated with metabolic dysregulation. Despite this, no study investigating short sleep and obesity has addressed the potential confounder of OSA. The aim of this study was to investigate the association between short sleep duration and obesity in children with and without OSA.

Methods

In this retrospective study, 306 children who underwent polysomnography between January and December 2010 were included. A diagnosis of OSA was made if the apnea/hypopnea index on polysomnography is ≥1. Typical sleep times were obtained by parental report. Short sleep duration was defined as a reduction of >1 h from the minimum total sleep time (TST) recommended for age from the National Sleep Foundation (NSF).

Results

Overall, 32 % were obese, 39.5 % had short sleep duration, and 78 % had OSA. Children with OSA had a similar frequency of short sleep duration than those without (39.6 vs. 42.4 %, p?=?0.950). In children with short sleep duration, the odds ratio for obesity was 2.5 (95 % CI 1.3–4.9; p?=?0.009) compared to children with TST within normal limits even after accounting for the presence of OSA.

Conclusion

A parental history of total sleep duration of only 1 h less than recommended per age by the NSF is associated with a higher risk for obesity in children independently of the presence of OSA.     

Association of microsomal epoxide hydrolase exon 3 Tyr113His and exon 4 His139Arg polymorphisms with gastric cancer in India

Background

Microsomal epoxide hydrolase, an important phase II xenobiotic enzyme, exhibits polymorphisms at exon 3 (Tyr113His [T/C]) and exon 4 (His139Arg [A/G]), which modulate enzyme activity; this may affect susceptibility to cancers. We studied association between these polymorphisms and gastric cancer (GC).

Methods

In a prospective study, 77 patients with GC, 50 with peptic ulcer, and 160 healthy controls (HC) were genotyped for exon 3 (PCR-RFLP followed by sequencing) and exon 4 (PCR-RFLP). Helicobacter pylori was considered to be present if two of three tests (histology, rapid urease test, and IgG antibody) were positive.

Results

Tyr113His and His139Arg genotypes and haplotypes were comparable among groups. 113His carriers were commoner among H. pylori-negative patients with GC than HC (p-value?=?0.019, odds ratio (OR)?=?2.5, 95 % confidence interval (CI)?=?1.2–5.4). Haplotype combination of exons 3 and 4 113Tyr-139Arg (TA) were associated with higher and reduced risk in patients with GC than HC in presence and absence of H. pylori (25 % vs. 11 %; p-value?=?0.033, OR?=?2.61, 95 % CI?=?1.08–6.3 and 11.6 % vs. 28.7 %; p-value?=?0.004, OR?=?0.33, 95 % CI?=?0.15–0.7, respectively).

Conclusions

Though 113Tyr-139Arg was associated with GC in presence of H. pylori, in its absence, it appeared to be protective. Exon 3, 113His, however, was associated with GC even in absence of H. pylori infection.