TAP1 I333V gene polymorphism and type 1 diabetes mellitus: a meta‐analysis of 2248 cases

Transporter associated with antigen processing 1 (TAP1) I333V gene polymorphism has been suggested to be associated with type 1 diabetes mellitus (T1DM) susceptibility. However, the results from individual studies are inconsistent. To explore the association of TAP1 I333V gene polymorphisms with T1DM, a meta‐analysis involving 2246 cases from 13 individual studies was conducted. The pooled odd ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by a fixed‐effect model. A significant relationship was observed between TAP1 I333V gene polymorphism and T1DM in allelic (OR: 1.35, 95% CI: 1.08–1.68, P = 0.007), dominant (OR: 1.462, 95% CI: 1.094–1.955, P = 0.010), homozygous (OR: 1.725, 95% CI: 1.082–2.752, P = 0.022), heterozygous (OR: 1.430, 95% CI: 1.048–1.951, P = 0.024) and additive (OR: 1.348, 95% CI: 1.084–1.676, P = 0.007) genetic models. No significant association between TAP1 I333V gene polymorphism and T1DM was detected in a recessive genetic model (OR: 1.384, 95% CI: 0.743–2.579, P = 0.306) in the entire population, especially among Caucasians. No significant association between them was found in an Asian or African population. TAP1 I333V gene polymorphism was significantly associated with increased T1DM risk. V allele carriers might be predisposed to T1DM susceptibility.     

Association of the variants in the BUD13‐ZNF259 genes and the risk of hyperlipidaemia

The single nucleotide polymorphisms (SNPs) in the BUD13 homolog (BUD13) and zinc finger protein 259 (ZNF259) genes have been associated with one or more serum lipid traits in the European populations. However, little is known about such association in the Chinese populations. Our objectives were to determine the association of the BUD13/ZNF259 SNPs and their haplotypes with hypercholesterolaemia (HCH)/hypertriglyceridaemia (HTG) and to identify the possible gene–gene interactions among these SNPs. Genotyping of 6 SNPs was performed in 634 hyperlipidaemic and 547 normolipidaemic participants. The ZNF259 rs2075290, ZNF259 rs964184 and BUD13 rs10790162 SNPs were significantly associated with serum lipid levels in both HCH and non‐HCH populations (P < 0.008–0.001). On single locus analysis, only BUD13 rs10790162 was associated with HCH (OR: 2.23, 95% CI: 1.05, 4.75, P = 0.015). The G‐G‐A‐A‐C‐C haplotype, carrying rs964184‐G‐allele, was associated with increased risk of HCH (OR: 1.35, 95% CI: 1.10, 1.66, P = 0.005) and HTG (OR: 1.75, 95% CI: 1.39, 2.21, P = 0.000). The A‐C‐G‐G‐C‐C and A‐C‐A‐G‐T‐C haplotypes, carrying rs964184‐C‐allele, were associated with reduced risk of HCH (OR: 0.77, 95% CI: 0.61, 0.99, P = 0.039 and OR: 0.66, 95% CI: 0.47, 0.94, P = 0.021 respectively). On multifactor dimensionality reduction analyses, the two‐ to three‐locus models showed a significant association with HCH and HTG (P < 0.01–0.001). The BUD13/ZNF259 SNPs, which were significant in the European populations, are also replicable in the Southern Chinese population. Moreover, inter‐locus interactions may exist among these SNPs. However, further functional studies are required to clarify how these SNPs and genes actually affect the serum lipid levels.     

Association study in eating disorders: TPH2 associates with anorexia nervosa and self‐induced vomiting

Twin studies suggest that genetic factors play a substantial role in anorexia nervosa (AN) and self‐induced vomiting (SV), a key symptom that is shared among different types of eating disorders (EDs). We investigated the association of 25 single nucleotide polymorphisms (SNPs), capturing 71–91% of the common variance in candidate genes, stathmin (STMN1), serotonin receptor 1D (HTR1D), tryptophan hydroxylase 2 (TPH2) and brain‐derived neurotrophic factor (BDNF), with AN and EDs characterized by regular SV. The first allele frequencies of all the SNPs were compared between a Dutch case group (182 AN, 149 EDs characterized by SV) and 607 controls. Associations rendering P‐values < 0.05 from this initial study were then tested for replication in a meta‐analysis with two additional independent ED case–control samples, together providing 887 AN cases, 306 cases with an ED characterized by SV and 1914 controls. A significant effect for the minor C‐allele of tryptophan hydroxylase 2 rs1473473 was observed for both AN [odds ratio (OR) = 1.30, 95% CI 1.08–1.57, P < 0.003] and EDs characterized by SV (OR = 1.52, 95% CI 1.28–2.04, P < 0.006). In the combined case group, a dominant effect was observed for rs1473473 (OR = 1.38, 95% CI 1.16–1.64, P < 0.0003). The meta‐analysis revealed that the tryptophan hydroxylase 2 polymorphism rs1473473 was associated with a higher risk for AN, EDs characterized by SV and for the combined group.     

Hepatitis C virus infection and the risk of Sjögren or sicca syndrome: a meta‐analysis

Previous studies have suggested an association between hepatitis C virus (HCV) infection and the development of Sjögren's syndrome (SS), also known as sicca syndrome. The main objective of this study was to summarize the existing evidence and quantitatively evaluate the association between hepatitis C virus infection and SS/sicca syndrome by performing a meta‐analysis of observational studies. MEDLINE and PubMed (January 1980–August 2013) were searched to identify relevant studies in English. Outcomes were calculated and are reported as odds risk (OR) and 95% CIs based on a random‐effects model. Heterogeneity was assessed with I² statistics. Quality assessment was performed with the Newcastle–Ottawa scale. Based on meta‐analysis of five cross‐sectional and five cohort studies, a significant positive relationship between HCV infection and development of SS/sicca syndrome was found, the pooled random effects OR being 3.31 (95% CI, 1.46–7.48; P < 0.001). In subset analyses, the studies that used European diagnostic criteria showed a higher summary OR than did studies that adopted other diagnostic criteria. When the data were stratified by source of controls, significant associations were also observed when healthy people (OR = 9.44; 95% CI = 2.67–33.40; P = 0.204) or subjects with hepatitis B virus infection (OR = 6.57; 95% CI = 1.21–35.57; P = 0.5) were used as controls, but not when the controls were hospital‐based (OR = 0.99; 95% CI = 0.61–1.61; P = 0.169). In summary, the findings suggest that HCV infection is associated with SS/sicca syndrome. The observed increased risk in studies in which European diagnostic criteria and healthy controls were used and the decreased risk in studies with hospital‐based controls may be attributable to selection bias or other unknown factors.     

Intracardiac injection of matrigel induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model

Matrigel promotes angiogenesis in the myocardium from ischemic injury and prevents remodelling of the left ventricle. We assessed the therapeutic efficacy of intracardiac matrigel injection and matrigel‐mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, matrigel (250 μl) or phosphate‐buffered solution (PBS) was delivered by intracardiac injection. Compared to the MI control group (MI‐PBS), matrigel significantly improved left ventricular function (n= 11, P < 0.05) assessed by pressure–volume loops after 4 weeks. There is no significant difference in infarct size between MI‐matrigel (MI‐M; 21.48 ± 1.49%, n= 10) and MI‐PBS hearts (20.98 ± 1.25%, n= 10). The infarct wall thickness of left ventricle is significantly higher (P < 0.01) in MI‐M (0.72 ± 0.02 mm, n= 10) compared with MI‐PBS (0.62 ± 0.02 mm, n= 10). MI‐M hearts exhibited higher capillary density (border 130.8 ± 4.7 versus 115.4 ± 6.0, P < 0.05; vessels per high‐power field [HPF; 400×], n= 6) than MI‐PBS hearts. c‐Kit⁺ stem cells (38.3 ± 5.3 versus 25.7 ± 1.5 c‐Kit⁺ cells per HPF [630×], n= 5, P < 0.05) and CD34⁺ cells (13.0 ± 1.51 versus 5.6 ± 0.68 CD34⁺ cells per HPF [630×], n= 5, P < 0.01) were significantly more numerous in MI‐M than in MI‐PBS in the infarcted hearts (n= 5, P < 0.05). Intracardiac matrigel injection restores myocardial functions following MI, which may attribute to the improved recruitment of CD34⁺ and c‐Kit⁺ stem cells.     

KCNQ1 rs2237892 C→T gene polymorphism and type 2 diabetes mellitus in the Asian population: a meta‐analysis of 15,736 patients

The KCNQ1 rs2237892 C→T gene polymorphism is reportedly associated with T2DM susceptibility, but various studies show conflicting results. To explore this association in the Asian population, a meta‐analysis of 15,736 patients from 10 individual studies was performed. The pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were evaluated using random‐effect or fixed‐effect models. A significant relationship between the KCNQ1 rs2237892 C→T gene polymorphism and T2DM was observed in the Asian population under the allelic (OR, 1.350; 95% CI, 1.240–1.480; P < 0.00001), recessive (OR: 0.650; 95% CI: 0.570–0.730; P < 0.00001), dominant (OR: 1.450; 95% CI: 1.286–1.634; P < 0.00001), and additive (OR: 1.346; 95% CI: 1.275–1.422; P < 0.00001) genetic models. In the subgroup analysis by race, a significant association was found in Chinese, Korean and Malaysia population, but not in Indian population. KCNQ1 rs2237892 C→T gene polymorphism was found to be significantly associated with increased T2DM risk in the Asian population, except Indian population. The C allele of the KCNQ1 rs2237892 C→T gene polymorphism may confer susceptibility to T2DM.     

Polymorphisms in the Melanocortin‐1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) Genes in Korean Vitiligo Patients

We have examined the frequency of SNP polymorphisms within the melanocortin‐1 receptor (MC1R) and agouti signaling protein (ASIP) genes in 114 Korean vitiligo patients and 111 normal controls to assess the association of these loci with vitiligo risk. Using direct sequencing techniques, we found the following five MC1R coding region SNPs: Arg67Gln (G200A), Val92Met (G274A), Ile120Thr (T359C), Arg160Arg (C478A), and Gln163Arg (A488G). Of these, the most common were Val92Met at 14% in patients vs. 9% in controls (P = 0.17) and Gln163Arg at 17% in patients vs. 17% in controls (P = 0.84). Presence of the A allele of Val92Met (G274A) was higher in vitiligo patients {P = 0.12, odds ratio (OR) [95% confidence interval (CI)] = 1.68 (0.86–3.25)}. The other three variants showed a frequency <5% of both patients and controls. The ASIP 3′UTR genotype (g.8818A‐G) was also assessed in the same subjects. The frequency of the G allele of 3′UTR in ASIP was 17% in vitiligo and 12% in controls [P = 0.14, OR (95% CI) = 1.49 (0.87–2.54)]. Carriage of the G allele was higher in vitiligo patients [P = 0.17, OR (95% CI) = 1.50 (0.83–2.72)], and those who also carried MC1R Val92Met were more prone to vitiligo [eight of 111 patients vs. four of 111 in controls, P = 0.14, OR (95% CI) = 2.75 (0.71–8.69)]. None of these associations, however, reached statistical significance.     

Dynamic changes of platelet-related parameters and their associations with clinical outcomes in COVID-19 patients during hospitalization

This paper aims to analyze dynamic changes in platelet-related indicators and their associations with clinical outcomes in COVID-19 patients. 220 COVID-19 patients hospitalized in the General Hospital of Central Theater Command the PLA from January 21, 2020 to March 25, 2020, were enrolled. These patients were firstly divided into non-severe and severe groups in accordance with disease severity on admission. The patients of the severe group were further divided into survivors and non-survivors according to whether the patient was discharged or deceased. The results demonstrated that IL-6 had negative correlations with PLT (R=?0.318, P<0.001) and PCT (R=?0.323, P<0.001). However, no significant correlations or only weak correlations were found between the platelet-related parameters (PLT, MPV, PDW, PCT, and P-LCR) and other indexes of coagulation and inflammation (PT, APTT, FIB, D-D, and CRP). The dynamic changes of platelet-related parameters in non-severe patients and survivors during hospitalization showed very similar trends and changing rules, while those in the non-survivor group were considerably different. After adjusting for demographic variables and coexisting disorders, the patients with nadir platelet counts of (100–150), (50–100), and (0–50), respectively, possessed a significantly increased risk of mortality [(OR=1.81, 95% CI, 0.2–16.44, P>0.05), (OR=9.91, 95% CI, 1.36–72.2, P<0.05), and (OR=53.81, 95% CI, 5.85–495.22, P<0.001)] with (150–) as the reference. This study suggests that changing trends of the platelet-related parameterrs during hospitalization especially in the first week after admission, are of great significance for predicting clinical outcomes.     

Characteristics of circulating CD31+ cells from patients with coronary artery disease

Recently, we reported the properties of CD31‐expressing cells in healthy individuals. However, the characteristics of CD31‐expressing cells derived from coronary artery disease (CAD) patients remain unknown. This study aimed to investigate the relationship between circulating CD31⁺ cells and CAD as well as their biological characteristics. Analysis with flow cytometry revealed that CD31⁺ cells (C‐CD31) from the peripheral blood (PB) of CAD patients exhibited low levels of T‐cell marker and high levels of macrophage marker compared with the PB‐CD31⁺ cells from healthy individuals (H‐CD31). In addition, the expression levels of multiple pro‐angiogenic and chemokine genes were significantly down‐regulated in C‐CD31. However, inflammatory gene IL‐1α was highly up‐regulated in C‐CD31. Patients with unstable angina (UA) had significantly more CD31⁺ cells in the PB than healthy control group (P < 0.001). Moreover, there were significant correlations between the number of CD31⁺ cells and cardiovascular (CV) disease activity (R = 0.318, P = 0.006) and the number of diseased coronaries (R = 0.312, P = 0.005). For the diagnostic category of UA, the area under curve was 0.803 (P < 0.001). In conclusion, C‐CD31 have impaired angiogenic potential and the number of circulating CD31⁺ cells were correlated with CV risk. These findings may contribute to the understanding of the pathogenesis of CAD.     

Body Fat Distribution and Inflammation Among Obese Older Adults With and Without Metabolic Syndrome

The protective mechanisms by which some obese individuals escape the detrimental metabolic consequences of obesity are not understood. This study examined differences in body fat distribution and adipocytokines in obese older persons with and without metabolic syndrome. Additionally, we examined whether adipocytokines mediate the association between body fat distribution and metabolic syndrome. Data were from 729 obese men and women (BMI ≥30 kg/m²), aged 70–79 participating in the Health, Aging and Body Composition (Health ABC) study. Thirty‐one percent of these obese men and women did not have metabolic syndrome. Obese persons with metabolic syndrome had significantly more abdominal visceral fat (men: P = 0.04; women: P < 0.01) and less thigh subcutaneous fat (men: P = 0.09; women: P < 0.01) than those without metabolic syndrome. Additionally, those with metabolic syndrome had significantly higher levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and plasminogen activator inhibitor‐1 (PAI‐1) than individuals without metabolic syndrome. Per standard deviation higher in visceral fat, the likelihood of metabolic syndrome significantly increased in women (odds ratio (OR): 2.16, 95% confidence interval (CI): 1.59–2.94). In contrast, the likelihood of metabolic syndrome decreased in both men (OR: 0.56, 95% CI: 0.39–0.80) and women (OR: 0.49, 95% CI: 0.34–0.69) with each standard deviation higher in thigh subcutaneous fat. These associations were partly mediated by adipocytokines; the association between thigh subcutaneous fat and metabolic syndrome was no longer significant in men. In summary, metabolically healthy obese older persons had a more favorable fat distribution, characterized by lower visceral fat and greater thigh subcutaneous fat and a more favorable inflammatory profile compared to their metabolically unhealthy obese counterparts.     

The Association of Restrained Eating With Weight Change Over Time in a Community‐Based Sample of Twins

We investigated the association of restrained eating with BMI and weight gain while controlling for the influence of genes and shared environment. Participants were 1,587 twins enrolled in the University of Washington Twin Registry (UWTR). Restrained eating was assessed by the Herman and Polivy Restraint Scale. Height and weight were self‐reported on two occasions. Analyses used generalized estimating equations or multiple linear regression techniques. Restraint Scale scores were positively associated with both BMI (adjusted β = 0.39 kg/m²; 95% confidence interval (CI) = 0.34–0.44; P < 0.001) and weight gain (adjusted β = 0.33 pounds; 95% CI = 0.17–0.49; P < 0.001). High Restraint Scale scorers had an adjusted mean BMI of 27.9 kg/m² (95% CI = 27.4–28.4) as compared to intermediate (mean = 25.5 kg/m²; 95% CI = 25.2–25.8) and low scorers (mean = 23.0 kg/m²; 95% CI = 22.7–23.3). In within‐pair analyses among 598 same‐sex twin pairs, the adjusted association between Restraint Scale scores and BMI persisted even when genetic and shared environmental factors were controlled for (adjusted β = 0.18; 95% CI = 0.12–0.24; P < 0.001), as did the association with weight gain (adjusted β = 0.37; 95% CI = 0.13–0.61; P = 0.003). In stratified analyses, dizygotic (DZ) twins differed more in BMI for a given difference in the Restraint Scale score than monozygotic (MZ) twins, for whom genetics are 100% controlled (adjusted β = 0.32; 95% CI = 0.20–0.44 vs. adjusted β = 0.10; 95% CI = 0.04–0.16; P = 0.001 for test of interaction). These data demonstrate that observed relationships between BMI, weight gain, and restrained eating, as assessed by the Restraint Scale, have a strong environmental influence and are not solely due to shared genetic factors.     

Emperipolesis mediated by CD8+ T cells correlates with biliary epithelia cell injury in primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell‐in‐cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty‐six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early‐stage PBC (stages I and II, n = 39) and late‐stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin‐eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3⁺ and CD8⁺ T cells correlated with the advancement of emperipolesis (R² = 0.318, P < .001; R² = 0.060, P < .05). The cell numbers of TUNEL‐positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R² = 0.236, P < .001; R² = 0.267, P < .001). We conclude that emperipolesis mediated by CD8⁺ T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts.     

Genetic predisposition of six well‐defined polymorphisms in HMGB1/RAGE pathway to breast cancer in a large Han Chinese population

Breast cancer constitutes an enormous burden in China. A strong familial clustering of breast cancer suggests a genetic component in its carcinogenesis. To examine the genetic predisposition of high mobility group box‐1/receptor for advanced glycation end products (HMGB1/RAGE) pathway to breast cancer, we genotyped six well‐defined polymorphisms in this pathway among 524 breast cancer patients and 518 cancer‐free controls from Heilongjiang province, China. There were no deviations from Hardy–Weinberg equilibrium for all polymorphisms. In single‐locus analysis, the frequency of rs1800624 polymorphism mutant A allele in RAGE gene was significantly higher in patients than in controls (24.52% versus 19.50%, P = 0.006), with the carriers of rs1800624‐A allele being 1.51 times more likely to develop breast cancer relative to those with rs1800624‐GG genotype after adjustment (95% confidence interval or CI: 1.17–1.94, P = 0.001). In HMGB1 gene, haplotype analysis did not reveal any significance, while in RAGE gene, haplotypes C‐T‐A and C‐A‐G (alleles in order of rs1800625, rs18006024, rs2070600) were significantly associated with an increased risk of breast cancer (adjusted OR = 2.72 and 10.35; 95% CI: 1.20–6.18 and 1.58–67.80; P = 0.017 and 0.015 respectively). In further genetic score analysis, per unit and quartile increments of unfavourable alleles were significantly associated with an increased risk of breast cancer after adjustment (odds ratio or OR = 1.20 and 1.26; 95% CI: 1.09–1.32 and 1.12–1.42; P < 0.001 and <0.001 respectively). Our findings altogether demonstrate a significant association between RAGE gene rs1800624 polymorphism and breast cancer risk, and more importantly a cumulative impact of multiple risk associated polymorphisms in HMGB1/RAGE pathway on breast carcinogenesis.     

Genetic polymorphism of heme oxygenase 1 promoter in the occurrence and severity of chronic obstructive pulmonary disease: a meta‐analysis

Heme oxygenase 1 (HMOX1) plays an important role in the development of chronic obstructive pulmonary disease (COPD). However, the association of HMOX1 length polymorphism in promoter region to the risk and severity of COPD has not been well studied. In this study, we searched the databases including PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) and extracted the information from related articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to study the effect of HMOX1 polymorphism on the risk and severity of COPD. As a result, nine studies were included for this meta‐analysis. Higher frequencies of L allele and type I genotype (containing at least one L allele) were found in patients with COPD (for L allele, OR 2.02, 95% CI: 1.32–3.11, P = 0.001; for type I genotype, OR 1.82, 95% CI: 1.28–2.61, P = 0.001), especially in Asian population (for L allele, OR 2.23, 95% CI: 1.68–2.95, P < 0.001; for type I genotype, OR 2.02, 95% CI: 1.51–2.70, P < 0.001). Genotyping method, source of control subjects, literature quality and language also affected the results to some extent. However, there was little difference in HMOX1 genotypes distribution in patients with COPD with different severity. Our study indicated L allele and type I genotype were related to the susceptibility but not the severity of COPD.     

Apo A5 −1131T/C, FgB −455G/A, −148C/T, and CETP TaqIB gene polymorphisms and coronary artery disease in the Chinese population: a meta-analysis of 15,055 subjects

The Apolipoprotein A5 (APO A5) ?1131T/C, fibrinogen β (FgB) ?455G/A, ?148C/T, and cholesteryl ester transfer protein (CETP) TaqIB gene polymorphisms have been indicated to be associated with the coronary artery disease (CAD) risk, but the individual study results are still inconsistent. To explore the relationship between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD in the Chinese population, the current meta-analysis involving 15,055 subjects from 40 individual studies was conducted. The pooled odds ratio (OR) for the association between APO A5 ?1131T/C, FgB ?455G/A, ?148C/T, and CETP TaqIB gene polymorphisms and CAD and its corresponding 95 % confidence interval (95 % CI) were evaluated by random or fixed effect model. A significant association between APO A5 ?1131T/C gene polymorphism and CAD in the Chinese population was found under an allelic (OR: 1.33, 95 % CI: 1.22–1.44, P < 0.00001), recessive (OR: 1.67, 95 % CI: 1.25–2.25, P = 0.0006), dominant (OR: 0.820, 95 % CI: 0.767–0.876, P = 1.0 × 10^?10), homozygous (OR: 2.36, 95 % CI: 1.55–3.58, P < 0.0001) and heterozygous genetic models (OR: 1.136, 95 % CI:1.075–1.200, P = 1.0 × 10^?10). A significant association between FgB ?455G/A gene polymorphism and CAD was also detected in the Chinese population under an allelic (OR: 1.50, 95 % CI: 1.25–1.81, P < 0.0001), dominant (OR: 0.864, 95 % CI: 0.819–0.912, P = 1.0 × 10^?10), homozygous (OR: 1.616, 95 % CI: 1.213–2.152, P = 0.001) and heterozygous genetic models (OR: 1.245, 95 % CI:1.138–1.361, P = 1.0 × 10^?10). No significant association was found between them under a recessive genetic model (OR: 1.124, 95 % CI: 0.844–1.497, P = 0.424). A significant association was also found between FgB ?148C/T gene polymorphism and CAD in the Chinese population under an allelic (OR: 1.34, 95 % CI: 1.06–1.71, P = 0.02), recessive (OR: 1. 65, 95 % CI: 1.02–2.69, P = 0.04), dominant (OR: 0.924, 95 % CI: 0.872–0.978, P = 0.007) and homozygous genetic models (OR: 0.968, 95 % CI: 0.942–0.995, P = 0.018). No significant association was found between them under a heterozygous genetic model (OR: 0.979, 95 % CI: 0.937–1.023, P = 0.342). In the whole Chinese population, no significant association between the CETP TaqIB gene polymorphism and CAD was found under an allelic (OR: 1.17, 95 % CI: 0.94–1.45, P = 0.15), dominant (OR: 1.46, 95 % CI: 0.80–2.67, P = 0.22) or recessive genetic models (OR: 0.68, 95 % CI: 0.32–1.44, P = 0.31). However, in the subgroup analysis stratified by ethnicity, there was a significant association between them under an allelic (OR: 1.27, 95 % CI: 1.07–1.52, P = 0.007) and dominant genetic model (OR: 2.04, 95 % CI: 1.49–2.79, P < 0.00001) in the Han subgroup. In the Chinese population, the APO A5 ?1131T/C and FgB ?455G/A, ?148C/T gene polymorphisms were implied to be associated with CAD susceptibility. The APO A5 ?1131C, FgB ?455A, and ?148T alleles might confer susceptibility to CAD. CETP TaqIB gene polymorphism was suggested to be associated with CAD susceptibility in the Chinese Han population. Carriers with B1 allele of CETP TaqIB gene might be predisposed to CAD in the Chinese Han population.     

Evidence of transmission ratio distortion of DLG5 R30Q variant in general and implication of an association with Crohn disease in men

Recently, we described the association of genetic variation in the discs large homolog 5 (DLG5) gene with inflammatory bowel disease (IBD) in a large European study sample (Stoll et al. in Nat Genet 36:476–480, 2004). Here, we report that the R30Q variant constitutes a susceptibility factor for Crohn disease (CD) in men [odds ratio (OR)=2.49, 95% confidence interval (CI) 1.53–4.06, P<0.001] but not women (OR=1.01, 95% CI=0.70–1.45, P=0.979) using multivariate logistic regression analyses in a unified study sample from Germany, Italy and Quebec. R30Q is a significant predictor for CD in men even when accounting for CARD15 and IBD5 risk variants (adjusted OR=2.41, 95% CI=1.41–4.12, P=0.001). The observed association is driven by a gender-dependent transmission ratio distortion (TRD) among healthy controls (frequency of Q allele: men 5.2%, women 11.3%), an effect that is offset in CD patients (frequency of Q allele: men 10.1%, women 10.9%). This finding is further substantiated by two non-IBD study samples, one of which consists of a newborn screening sample (newborn males 7.1%; newborn females 11%, P=0.036). Further investigation of the observed TRD may contribute towards enlightening the role of DLG5 in physiological processes influencing transmission of chromosomes to the surviving offspring, which, in turn, may help in understanding its implication in the development of CD among men.Frauke Friedrichs and Sonia Brescianini equally contributed to the work.     

Single‐nucleotide Polymorphism of CD36 Locus and Obesity in European Adolescents

CD36 is a membrane receptor with a wide variety of functions, including the regulation of energy metabolism, fat storage, and adipocyte differentiation. To assess the relationship between CD36 gene single‐nucleotide polymorphisms (SNPs) and obesity in adolescents, we evaluated the relationship between CD36 SNPs and the risk of obesity in a case–control study composed of 307 obese (age = 15.0 ± 1.1 years) and 339 normal‐weight adolescents (age = 14.6 ± 1.1 years). To validate the results, we assessed the relation between the same SNPs and percentage of body fat (BF%) and BMI in 1,151 European adolescents (age = 14.8 ± 1.4 years). SNPs with a minor allele frequency >0.10 were selected to tag CD36. Genotyping was performed on an Illumina system. Four SNPs (rs3211867, rs3211883, rs3211908, and rs1527483) were associated with increased risk of obesity in the case–control study (odds ratio (OR) (95% confidence interval)): 1.96 (1.26–3.04], P = 0.003; 1.73 (1.16–2.59), P = 0.007; 2.42 (1.47–4.01), P = 0.0005 and 1.95 (1.25–3.05), P = 0.003, respectively). The same four SNPs were associated with higher BMI (P < 0.05) and BF% (P < 0.04) in the validation study. Further analyses identified a haplotype (frequency: 0.05) carrying the minor allele of these SNPs as being associated with obesity (OR: 2.28; P = 0.0008) in the case–control study and with excess adiposity (i.e., higher BF% (P = 0.03) and BMI (P = 0.04)) in the validation study. Our data suggest that genetic variability at the CD36 gene locus could be associated with body weight variability in European adolescents but these findings require replication.     

Association of interleukin‐27 gene polymorphisms with susceptibility to HIV infection and disease progression

Interleukin‐27 (IL‐27) gene polymorphisms are linked to infectious disease susceptibility and IL‐27 plasma level is associated with HIV infection. Therefore, we aimed to investigate the association between IL‐27 polymorphisms and susceptibility to HIV infection and disease progression. A total of 300 patients with HIV infection (48 long‐term nonprogressors and 252 typical progressors) and 300 healthy controls were genotyped for three IL‐27 polymorphisms, rs17855750, rs181206, rs40837 which were performed by using multiple single nucleotide primer extension technique. Significant association was found between IL‐27 rs40837 polymorphisms with susceptibility to HIV infection (AG vs AA: adjusted OR = 1.60, 95% CI, 1.11‐2.30, P = 0.012; AG+GG vs AA: adjusted OR = 1.44, 95% CI, 1.02‐2.03, P = 0.038) and disease progression (LTNP: AG vs AA: adjusted OR = 2.33, 95% CI, 1.13‐4.80, P = 0.021; TP: AG vs AA: adjusted OR = 1.50, 95% CI, 1.04‐2.24, P = 0.030). Serum IL‐27 levels were significantly lower in cases compared to controls (P < 0.001). There were lower serum IL‐27 levels in TPs than in LTNPs (P < 0.001). We further found that LTNPs with rs40837 AG or GG genotype had lower serum IL‐27 levels than with AA genotype (P < 0.05). The CD4⁺T counts in cases were significantly lower than controls (P < 0.001). In contrast, individuals with rs40837 AG genotype had lower CD4⁺T counts than with AA genotype in cases (P < 0.05). In addition, CD4⁺T counts in TPs were significantly lower than LTNPs (P < 0.001). IL‐27 rs40837 polymorphism might influence the susceptibility to HIV infection and disease progression probably by regulating the level of serum IL‐27 or the quantity of CD4⁺T.