Is Sp1 binding site polymorphism within COL1A1 gene associated with tennis elbow?

Tennis elbow defines a condition of pain and tenderness over the lateral epicondyle of the humerus. The exact aetiology of the injury is not yet fully understood. The major constituent of tendons is type 1 collagen which is encoded by COL1A1 gene. The aim of the study was to determine whether Sp1 binding site polymorphism (SNP rs1800012; 1546G/T) within the intronic region of COL1A1 gene is associated with tennis elbow. One hundred and three tennis elbow patients and one hundred and three healthy subjects without any history of previous ligament or tendon injuries were recruited for this genetic association study. All participants were genotyped for the COL1A1 Sp1 binding site polymorphism by using PCR–RFLP method. There were no observed statistical differences in the genotype (p = 0.17) or allele (p = 0.11) distributions between the groups. G allele frequency in patients and controls was 82.5% and 76.21%, and T allele frequency was 17.5% and 23.79% respectively. This study has shown that there is no association between this polymorphism and tennis elbow within the population studied.     

Is early osteoarthritis associated with differences in joint congruence?

Previous studies suggest that osteoarthritis (OA) is related to abnormal or excessive articular contact stress. The peak pressure resulting from an applied load is determined by many factors, among which is shape and relative position and orientation of the articulating surfaces or, referring to a more common nomenclature, joint congruence. It has been hypothesized that anatomical differences may be among the causes of OA. Individuals with less congruent joints would likely develop higher peak pressure and thus would be more exposed to the risk of OA onset. The aim of this work was to determine if the congruence of the first carpometacarpal (CMC) joint differs with the early onset of OA or with sex, as the female population has a higher incidence of OA. 59 without and 38 with early OA were CT-scanned with their dominant or arthritic hand in a neutral configuration. The proposed measure of joint congruence is both shape and size dependent. The correlation of joint congruence with pathology and sex was analyzed both before and after normalization for joint size. We found a significant correlation between joint congruence and sex due to the sex-related differences in size. The observed correlation disappeared after normalization. Although joint congruence increased with size, it did not correlate significantly with the onset of early OA. Differences in joint congruence in this population may not be a primary cause of OA onset or predisposition, at least for the CMC joint.     

Is the ApoE polymorphism associated with dilated cardiomyopathy?

Apolipoprotein E (ApoE) is 34 kDa protein involved in the modulation of cholesterol transport and homeostasis. Polymorphism of the ApoE gene has been implicated in many chronic cardiovascular and neuronal diseases. ApoE epsilon4 allele has been reported to be associated with increased risk of cardiovascular diseases such as myocardial infarction, hypertension, coronary heart disease, etc. Fifty patients with the end-stage dilated cardiomyopathy (DCM) and advanced congestive heart failure were examined in our study. For evaluation of ApoE polymorphism, novel approach of fast screening of ApoE gene polymorphism by combination of PCR and blotting (CVD StripAssay) was used. Individual genotypes were correlated with basic cardiologic clinical parameters. The reported frequency of this allele in Caucasian population is 14.7 %. Our results showed that in patients with DCM frequency of the ApoE epsilon4 allele is 40 %. Frequency of the genotype epsilon2/4 was 58 % and epsilon3/4 was 22 %. Comparison with control Caucasian groups monitored by others clearly revealed that frequency of epsilon4 alelle is increased in patients with advanced stages of DCM. This observation suggests association of ApoE polymorphism with severe form of DCM. Physiological consequences of this observation remain to be clarified.     

Is A163G polymorphism in the osteoprotegerin gene associated with heel velocity of sound in postmenopausal women?

Osteoprotegerin (OPG) plays an important inhibitory role in osteoclastogenesis. Polymorphisms in the OPG gene recently have been associated with various bone phenotypes including fractures. The aim of the present study was to investigate the association between three informative OPG polymorphisms and quantitative ultrasound variables of the heel. In a cohort of 165 perimenopausal women polymorphisms in the OPG promoter (A163G, T245G) and in exon 1 (G1181C) were assessed by PCR-RFLP analysis. The distribution of the investigated genotypes was similar to other Caucasian women (A163G-AA 68 %, AG 30 %, GG 2 %, T245G-TT 84.4 %, TG 15 %, GG 0.6 %, G1181C- GG 22 %, CG 55 %, CC 23 %). After adjustment for body mass index and years since menopause, in a subgroup of 87 postmenopausal subjects, calcaneal velocity of sound (VOS, m/s) was significantly associated with A163G polymorphism (p=0.0102, ANCOVA). Women with the presence of G allele (AG+GG genotypes) had significantly lower VOS than women with AA genotype. Neither T245G nor G1181C were associated with calcaneal ultrasound indices. In conclusion, A163G polymorphism was significantly associated with VOS at the heel in a limited cohort of postmenopausal women. The present study replicated in part the previous findings about OPG gene variations and peripheral bone mass in Caucasian women.     

Polymorphisms in the 5′ regulatory region of myostatin gene are associated with early growth traits in Yorkshire pigs

Myostatin is a negative regulator of skeletal muscle mass. The present study cloned the 5' regulatory region of porcine myostatin gene, screened its polymorphisms and analyzed their associations with early growth traits in Yorkshire pigs. The results indicated that a fragment length polymorphism and a polymorphism concerning two nucleotide changes exist in the 5' regulatory region of porcine myostatin gene. At sites 435 and 447, allele A and allele B have the haplotypes of A-G and G-A, respectively. The allelic frequency of B is 0.475 in Yorkshire pigs. No homozygous BB genotype was detected in 9 Laiwu Black pigs. Allele B was found to have positive effect on body weight on day 21 (BW21) (P＜0.01), body weight on day 28 (BW28) (P＜0.05), body weight on day 70 (BW70) (P＜0.05), average daily gain from birth to 21 d (ADG1) (P＜0.01), average daily gain from birth to 28 d (ADG2) (P＜0.05) and average daily gain from 21 d to 70 d (ADG3) (P＜0.01), respectively. The additive effect of allele B on BW21, BW28, BW70, ADG1, ADG2 and ADG3 was 0.596±0.205 kg (P=0.0041), 0.498±0.200 kg (P=0.0136), 1.409±0.551 kg (P=0.0112), 28.39±9.74 g P=0.0041), 17.78±7.15 g (P=0.0136) and 37.00±16.92 g (P=0.0304), respectively, whereas its effect on average daily gain from 28 d to 70 d (ADG4) was not significant (P＞0.1), although BB individuals are superior in average daily gain to AA and AB.     

Polymorphisms in the 5 ′ regulatory region of my-ostatin gene are associated with early growth traits in Yorkshire pigs

Myostatin is a negative regulator of skeletal muscle mass. The present study cloned the 5′ regulatory region of porcine myostatin gene, screened its polymorphisms and analyzed their associations with early growth traits in Yorkshire pigs. The results indicated that a fragment length polymorphism and a polymorphism concerning two nucleotide changes exist in the 5′ regulatory region of porcine my-ostatin gene. At sites 435 and 447, allele A and allele B have the haplotypes of A-G and G-A, respec-tively. The allelic frequency of B is 0.475 in Yorkshire pigs. No homozygous BB genotype was detected in 9 Laiwu Black pigs. Allele B was found to have positive effect on body weight on day 21 (BW21) (P<0.01), body weight on day 28 (BW28) (P<0.05), body weight on day 70 (BW70) (P<0.05), average daily gain from birth to 21 d (ADG1) (P<0.01), average daily gain from birth to 28 d (ADG2) (P<0.05) and av-erage daily gain from 21 d to 70 d (ADG3) (P<0.01), respectively. The additive effect of allele B on BW21, BW28, BW70, ADG1, ADG2 and ADG3 was 0.596±0.205 kg (P=0.0041), 0.498±0.200 kg (P=0.0136), 1.409±0.551 kg (P=0.0112), 28.39±9.74 g P=0.0041), 17.78±7.15 g (P=0.0136) and 37.00±16.92 g (P=0.0304), respectively, whereas its effect on average daily gain from 28 d to 70 d (ADG4) was not significant (P>0.1), although BB individuals are superior in average daily gain to AA and AB.     

Polymorphisms in the 5′ regulatory region of myostatin gene are associated with early growth traits in Yorkshire pigs

Myostatin is a negative regulator of skeletal muscle mass. The present study cloned the 5′ regulatory region of porcine myostatin gene, screened its polymorphisms and analyzed their associations with early growth traits in Yorkshire pigs. The results indicated that a fragment length polymorphism and a polymorphism concerning two nucleotide changes exist in the 5′ regulatory region of porcine myostatin gene. At sites 435 and 447, allele A and allele B have the haplotypes of A-G and G-A, respectively. The allelic frequency of B is 0.475 in Yorkshire pigs. No homozygous BB genotype was detected in 9 Laiwu Black pigs. Allele B was found to have positive effect on body weight on day 21 (BW21) (P<0.01), body weight on day 28 (BW28) (P<0.05), body weight on day 70 (BW70) (P<0.05), average daily gain from birth to 21 d (ADG1) (P<0.01), average daily gain from birth to 28 d (ADG2) (P<0.05) and average daily gain from 21 d to 70 d (ADG3) (P<0.01), respectively. The additive effect of allele B on BW21, BW28, BW70, ADG1, ADG2 and ADG3 was 0.596±0.205 kg (P=0.0041), 0.498±0.200 kg (P=0.0136), 1.409±0.551 kg (P=0.0112), 28.39±9.74 g P=0.0041), 17.78±7.15 g (P=0.0136) and 37.00±16.92 g (P=0.0304), respectively, whereas its effect on average daily gain from 28 d to 70 d (ADG4) was not significant (P>0.1), although BB individuals are superior in average daily gain to AA and AB.     

Is Saccharomyces cerevisiae apoptotic cell death associated with gene transfer?

Programmed cell death in unicellular organisms is difficult to account for in evolutionary terms. In the budding yeast, Saccharomyces cerevisiae, existence of several morphological and biochemical features of apoptosis has been described, and genes responsible for execution of the death program have been identified. It is here suggested that apoptosis of yeast cells could provide direct benefit to the genes of the dying cells, by facilitating DNA transfer to surrounding cells. The biochemical details of yeast apoptotic death are considered in light of a gene transfer hypothesis.     

A functional polymorphism in interleukin-1α (IL1A) gene is associated with risk of alopecia areata in Chinese populations

Alopecia areata (AA) is an inflammatory hair loss disorder with a major genetic component, which may cause great psychosocial distress for those affected. Studies have shown that interleukin-1 (IL-1) is a very potent inducer of hair loss and a significant human hair growth inhibitor. The 4-bp insertion/deletion (Indel) polymorphism (rs3783553) within the 3′ untranslated regions of IL1A gene has been suggested to be associated with risk of various types of cancers, possibly through regulating expression of IL-1α levels. In the current study, we estimated the susceptibility to AA associated with rs3783553 in two independent case–control panels of Eastern and Southern Chinese populations, totally containing 313 AA cases and 626 healthy controls. Logistic regression analysis showed that the heterozygote and the homozygote 4-bp ins/ins confer a significantly lower risk of AA in both panels and total subjects [odds ratio (OR) = 0.55, 95% confidence interval (C.I.) = 0.41–0.75, P = 6.24 × 10^− 5; OR = 0.47, 95% C.I. = 0.28–0.76, P = 0.001, respectively]. Stratification analysis based on age onset showed that the protective roles of ins/del and ins/ins genotype against developing AA was more obvious in AA patients with early age onset (< 30 years) under dominant model (OR = 0.48, 95% C.I. = 0.29–0.77, P = 0.001). The results of luciferase assay showed that rs3783553 could influence expression of IL-1α in a miR-122 dependant manner. Taken together, our results suggested that the IL1A 4-bp indel polymorphism may be a marker for genetic susceptibility to patchy (mild) AA in Chinese populations, likely through miR-122 mediated regulation.     

Is interleukin-10 gene polymorphism a predictive marker in HCV infection?

The clinical outcome of hepatitis C virus (HCV) infection varies between individuals - from spontaneous viral clearance and persistence without complication, to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Also patterns of response to interferon-based anti-HCV therapy are different from person to person. This diversity may be affected by host genetic factors, including alterations in genes encoding cytokines. Interleukin-10, as an anti-inflammatory cytokine and immune response modulator, may influence on HCV infection susceptibility as well as spontaneous and treatment-induced HCV eradication. Moreover, it is stated that IL-10 has antifibrotic properties and play a role in progression of liver disease. This review summarized studies on interleukin-10 gene polymorphisms (mainly promoter SNPs at positions -1082(G/A), -819(C/T) and -592(C/A)), which may determine IL-10 production, regarding susceptibility to HCV infection, course of HCV-related liver disease (fibrosis, cirrhosis, hepatocellular carcinoma, ALT abnormalities), spontaneous viral elimination as well as hepatitis C treatment outcomes. Analysis of hereby summarized studies shows that it is difficult to unambiguously determine the importance of IL-10 polymorphism as a predictor of clinical outcome of hepatitis C and response to anti-HCV therapy before its beginning. Thus, future larger studies need to address these issues. Continuation of studies on interleukin-10 polymorphisms as well as identification of other candidate predictive markers in HCV infection has important practical implications and there is a chance that may contribute to reduce the scale of hepatitis C problem.     

Is circadian type associated with sleep duration in twins?

Sleep and Biological Rhythms - We used the community-based University of Washington Twin Registry to investigate the genetic association between circadian type and sleep duration. Habitual sleep...     

Is the shift in chronotype associated with an alteration in well-being?

The study aimed to test whether a shift in chronotype (determined by mid-sleep on free days) is associated with alterations in psychological well-being and sleep parameters. One hundred and seventeen undergraduates were tested in longitudinal study with four repeated measures. Measurements were taken during spring in three-week intervals and each measurement consisted of self-reported sleep parameters on work and free days (i.e. bedtime, sleep latency, wake time, sleep onset, mid-sleep time, social jetlag), satisfaction with life, and mood (energetic arousal, tense arousal, hedonic tone). Between-subjects analyses revealed earlier chronotypes, as compared to the later ones, showing lower tense arousal, higher energetic arousal and life satisfaction, earlier bedtime, sleep onset and offset on both work and free days, longer sleep duration and shorter sleep latency on workdays, and less social jetlag. Within-subjects analyses revealed increasing photoperiod associated with a shift toward earlier chronotype, decrease in social jetlag, and shortening sleep latency. The seasonal shift toward earlier chronotype was not associated with alterations in mood or life satisfaction, but it was associated with a shift toward earlier bedtimes and longer sleep duration on workdays, decrease in sleep latency, and social jetlag. Results from the within-subjects analyses were consistent with the results of between-subjects analyses regarding sleep–wake functioning, but inconsistent regarding psychological outcomes.     

Is paraoxonase 192 gene polymorphism a risk factor for membranoproliferative glomerulonephritis in children?

We investigated the effects of paraoxonase (PON1) 192 polymorphism on serum PON1 activity and the impact of phenotypic expression on the risk and prognosis of Turkish children with membranoproliferative glomerulonephritis (MPGN). Eighteen children with biopsy-proven Type I MPGN (10 boys, 8 girls) and age-matched 53 healthy controls were included in the study. PCR (polymerase chain reaction), RFLP (restriction fragment length polymorphism) and agarose gel electrophoresis techniques were used to determine the PON1 192 genotype. PON1 activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON1 192 genotype distribution (AA, AB, BB) in MPGN patients were 61.1%, 22.3%, 16.6% and 15.1%, 35.8%, 49.1% in controls, respectively. The frequency of AA genotypes was significantly higher in the MPGN group (0.611) compared with the healthy controls (0.151) (p < 0.001). Although the serum PON1 activity was lower in MPGN patients (103.3 +/- 55.2 U/l) than the healthy controls (130.9 +/- 71.2 U/mol), the difference was not statistically significant (p = 0.0563). In the genotypes of patients and controls classified according to PON1 A/B polymorphism; serum PON1 activities were significantly increased (p < 0.001, ANOVA) in the order of PON1 AA, AB and BB in both MPGN patients (82.4, 91.7 and 173.6 U/l) and healthy controls (85.9, 119.9 and 193.1 U/l), respectively. There was a significant relationship between the poor prognosis and having AA genotype and low PON1 activity. Of the 8 patients with poor prognosis, 7 had genotype AA and the remaining one was AB heterozygote. Our results suggest that homozygosity for the A allele might have an important role on the risk for developing MPGN and may also be associated with the poor prognosis of disease. In conclusion, we suggest that the PON1 activities are affected by PON1 genetic variability in Turkish patients with MPGN.     

Is expression of aquaporins (plasma membrane intrinsic protein 2s, PIP2s) associated with thermonasty (leaf-curling) in Rhododendron?

It is postulated that leaf thermonasty (leaf curling) in rhododendrons under sub-freezing temperatures is caused by water redistribution due to extracellular freezing. We hypothesize that aquaporins (AQPs), the transmembrane water-channels, may be involved in regulating water redistribution and thus leaf curling. Our experimental system includes two Rhododendron species with contrasting leaf curling behavior whereby it was observed in R. catawbiense but not in R. ponticum. We compared leaf movements and the expression of two AQPs, i.e. R. catawbiense/ponticum plasma-membrane intrinsic protein 2 (Rc/RpPIP2;1 and Rc/RpPIP2;2), in the two species under freezing–rewarming and dehydration–rehydration cycles. To determine the relationship between extracellular freezing and leaf-curling, we monitored leaf-curling in R. catawbiense with or without controlled ice-nucleation. Our data indicate that extracellular freezing may be required for leaf curling. Moreover, in both species, PIP2s were up-regulated at temperatures that fell in ice-nucleation temperature range. Such up-regulation could be associated with the bulk-water efflux caused by extracellular freezing. When leaves were frozen beyond the ice-nucleation temperature range, PIP2s were continuously down-regulated in R. catawbiense along with the progressive leaf curling, as also observed for RcPIP2;2 in dehydrated leaves; as leaves uncurled during re-warming/rehydration, RcPIP2 expression was restored. On the other hand, R. ponticum, a non-curling species, exhibited substantial up-regulation of RpPIP2s during freezing/dehydration. Taken together, our data suggest that RcPIP2 down-regulation was associated with leaf curling. Moreover, the contrasting PIP2 expression patterns combined with leaf behavior of R. catawbiense and R. ponticum under these two cycles may reflect different strategies employed by these two species to tolerate/resist cellular dehydration.     

Deletions in the Parkin gene and genetic heterogeneity in a Greek family with early onset Parkinson’s disease

Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease and is manifested as a movement disorder. A positive family history is the second most important risk factor for developing the illness, after age. Both autosomal dominant and recessive forms of the illness have been described. Recently deletions in a novel gene, parkin, have been associated with the autosomal recessive form of the illness in Japanese families. In this study, we demonstrate that deletions of exons 5, 6 and 7 of the parkin gene are present in two affected individuals of a Greek pedigree with early onset Parkinson’s disease. However, no deletions were identified in a different branch of the same pedigree with three affected individuals. These results suggest that deletions in the parkin gene will be found in other families besides those of Japanese origin and that there must be at least one additional locus responsible for early onset autosomal recessive Parkinson’s disease. Received: 9 June 1998 / Accepted: 10 August 1998     

Is sociality associated with high longevity in North American birds?

Sociality, as a life-history trait, should be associated with high longevity because complex sociality is characterized by reproductive suppression, delayed breeding, increased care and survival, and some of these traits select for high longevity. We studied the relationship between cooperative parental care (a proxy of complex sociality) and relative maximum lifespan in 257 North American bird species. After controlling for variation in maximum lifespan explained by body mass, sampling effort, latitude, mortality rate, migration distance and age at first reproduction, we found no significant effect of cooperative care on longevity in analyses of species-specific data or phylogenetically independent standardized linear contrasts. Thus, sociality itself is not associated with high longevity. Rather, longevity is correlated with increased body size, survival rate and age of first reproduction.     

An insertion/deletion polymorphism in the 3′ untranslated region of β-transducin repeat-containing protein (βTrCP) is associated with susceptibility for hepatocellular carcinoma in Chinese

Hepatocellular carcinoma (HCC) is an epithelial cancer which originates from hepatocytes or their progenitors. As a positive regulator of NFκB signaling pathway, β-transducin repeat-containing protein (βTrCP) is overexpressed and oncogenic in epithelial cancers, suggesting a potential role of βTrCP in HCC susceptibility. We carried out a case-control study in a Chinese population (256 cases and 367 controls) to estimate the susceptibility to HCC associated with a 9 bp insertion/deletion polymorphism (rs16405) in 3′ untranslated region of βTrCP. Using unconditional logistic regression, we found that 9N del/del and 9N ins/del genotypes were significantly associated with decreased HCC risk: OR = 0.44 (0.24-0.83) (p = 0.004) and OR = 0.56 (0.31-1.00) (p = 0.034), respectively. Furthermore, in vivo experiments showed that mRNA levels of βTrCP from HCC tumor tissues were correlated with rs16405 genotypes. HCC tumor tissues with homozygous for 9N ins/ins has the highest level of βTrCP, which are 3.99 and 7.04-fold higher than heterozygous 9N ins/del and homozygous 9N del/del, respectively. Based on bioinformatics prediction, we found that the risk allele for rs16405 disrupted a binding site for human microRNA-920 which would negatively regulate βTrCP. We propose a microRNA-920 mediated βTrCP regulation model depending on rs16405 genotype, which warrants further replication association studies and follow-up functional experiments.