scholarly journals Sex differences in disease genetics

2016 ◽  
Author(s):  
William P. Gilks
Keyword(s):  
Gene Expression ◽  
Type Ii Diabetes ◽  
Disease Risk ◽  
Genetic Effect ◽  
Genetic Effects ◽  
List Type ◽  
Type Ii ◽  
Genome Wide ◽  
Inflammatory Bowel ◽  
Males And Females

AbstractThere is long-standing evidence for gene-by-sex interactions in disease risk, which can now be tested in genome-wide association studies with participant numbers in the hundreds of thousands. Contemporary methods start with a separate test for each sex, but simulations suggest a more powerful approach should be to use sex as an interaction term in a single test. The traits currently with the most compelling evidence for sex-dependent genetic effects are for adiposity (predictive of cardiac disease), type II diabetes, asthma and inflammatory bowel disease. Sexually dimorphic gene expression varies dynamically, by age, tissue type, and chromosome, so sex dependent genetic effects are expected for a wide range of diseases.Key conceptsCompelling findings of sex-dependent genetic effects on disease have been made in adiposity-related anthropometric traits, type II diabetes, and inflammatory bowel disease. Other disorders remain to be more fully investigated, regardless of what sexual differences they exhibit in prevalence and presentation.Current evidence indicates that sex difference in gene expression is not required for a SNP to have a sex-dependent effect. However, sex differences in gene expression vary dynamically, by organ and age, so generalisations may be inaccurate without comprehensive data.Sex-dependent risk alleles are predicted to be of greater effect size than conventional ones, because natural selection acts only against the sex which has the disease. There is evidence for this from a high-powered GWAS of adiposity-related traits.Many of the large GWAS meta-analyses look for sex-dependent genetic effects by testing male and female groups separately. However, this may be under-powered compared to a whole-sample, gene-by-sex interaction test.GlossaryGenome-wide association study (GWAS). Method for identifying molecular genetic variation that controls heritable traits, in a population sample. Involves assessing the correlation between allele frequencies and phenotype value, at millions of markers of common genetic variation across the genome.Sexual dimorphism. A difference between males and females in a population for the value of a particular trait. May include anything from anatomical measurements to expression level of a gene.Sex-dependent genetic effect. A disease risk allele is termed sex-specific when it increases risk in one sex only but has no effect on the disease in the other sex. The term sex-biased is used for an allele causes a significant increase in risk of disease in both sexes, but for which the magnitude of the risk increase is significantly different between males and females. There are also reports where an allele that increases risk of a disease in one sex reduces risk of the same disease in the other sex but none have been replicated, and there is no biochemical reason why this could be true. It effectively constitutes a sexually antagonistic effect, but should be distinguished from intra-locus sexual conflict which explicitly requires than an allele have opposing effects on the evolutionary fitness of males and females (Bonduriansky and Chenoweth 2009). All of the above relationships constitute a form of sex-dependent genetic effect.

Low‐fat diet: case study of a cardiology patient

2010 ◽  
Vol 40 (2) ◽  
pp. 235-242 ◽  
Author(s):  
Tanefa A. Apekey ◽  
Anne J.E. Morris ◽  
Shamusi Fagbemi ◽  
G.J. Griffiths
Keyword(s):  
Cardiovascular Disease ◽  
Pulse Rate ◽  
Type Ii Diabetes ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Type Ii ◽  
Low Fat ◽  
Content Type ◽  
Low Fat Diet

PurposeHealthy diet and lifestyle have been shown to be important for obese patients in the management of diet‐related diseases especially in the improvement of cardiovascular disease risk indicators. The purpose of this paper is to determine the effects of a calorie‐restricted low‐fat diet on body weight, cardiovascular disease risk and liver function indicators in an obese, cardiology outpatient with type II diabetes.Design/methodology/approachA male, obese cardiology outpatient was assigned to a calorie‐restricted (6,694.4 kJ/d) low‐fat (not to exceed 20 per cent of total energy intake) diet for 12 weeks. His body mass index (BMI), blood pressure (BP), pulse rate, fasting glucose, total cholesterol, triglyceride, low‐density lipoprotein cholesterol, high‐density lipoprotein (HDL) cholesterol, alanine aminotranseferase, aspartate aminotranseferase (AST) concentration and TC/HDL ratio were measured prior to the start of the diet and during weeks four, eight and 12 of the diet.FindingsThe patient found it difficult making changes to his diet and only reduced his weight by 1 kg. He significantly reduced his serum triglyceride by about 20 per cent, TC/HDL ratio by 13 per cent and fasting blood glucose concentration by 31 per cent. However, there was no significant change in his BP, pulse rate, total and LDL cholesterol concentration. He also reduced his AST concentration by 20 per cent and alanine aminotranseferase (ALT) by 19 per cent.Originality/valueThis paper usefully shows how healthier food choices involving increased intake of fruits and vegetables and restricted intake of total and saturated fat reduced the risk of cardiovascular death in a male cardiology outpatient with type II diabetes.

Mest/Peg1 imprinted gene enlarges adipocytes and is a marker of adipocyte size

2005 ◽  
Vol 288 (1) ◽  
pp. E117-E124 ◽  
Author(s):  
Mayumi Takahashi ◽  
Yasutomi Kamei ◽  
Osamu Ezaki
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Transgenic Mice ◽  
Type Ii Diabetes ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Peroxisome Proliferator ◽  
Type Ii ◽  
Fatty Acid Binding ◽  
Enhanced Expression

Obesity is a common and serious metabolic disorder in the developed world that is occasionally accompanied by type II diabetes, atherosclerosis, hypertension, and hyperlipidemia. We have found that mesoderm-specific transcript (Mest)/paternally expressed gene 1 (Peg1) gene expression was markedly enhanced in white adipose tissue of mice with diet-induced and genetically caused obesity/diabetes but not with streptozotocin-induced diabetes, which does not cause obesity. Administration of pioglitazone, a drug for type II diabetes and activator of peroxisome proliferator-activated receptor (PPAR)γ, in obese db/ db mice reduced the enhanced expression of Mest mRNA in adipose tissue, concomitant with an increase in body weight and a decrease in the size of adipose cells. Ectopic expression of Mest in 3T3-L1 cells caused increased gene expression of adipose markers such as PPARγ, CCAAT/enhancer binding protein (C/EBP)α, and adipocyte fatty acid binding protein (aP)2. In transgenic mice overexpressing Mest in adipose tissue, enhanced expression of the adipose genes was observed. Moreover, adipocytes were markedly enlarged in the transgenic mice. Thus Mest appears to enlarge adipocytes and could be a novel marker of the size of adipocytes.

scholarly journals Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3618 ◽  
Author(s):  
Rana Dajani ◽  
Jin Li ◽  
Zhi Wei ◽  
Michael E. March ◽  
Qianghua Xia ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Type Ii ◽  
Arab Population ◽  
Public Health Burden ◽  
Link Type ◽  
Genome Wide

The prevalence of Type II Diabetes (T2D) has been increasing and has become a disease of significant public health burden in Jordan. None of the previous genome-wide association studies (GWAS) have specifically investigated the Middle East populations. The Circassian and Chechen communities in Jordan represent unique populations that are genetically distinct from the Arab population and other populations in the Caucasus. Prevalence of T2D is very high in both the Circassian and Chechen communities in Jordan despite low obesity prevalence. We conducted GWAS on T2D in these two populations and further performed meta-analysis of the results. We identified a novel T2D locus at chr20p12.2 at genome-wide significance (rs6134031, P = 1.12 × 10−8) and we replicated the results in the Wellcome Trust Case Control Consortium (WTCCC) dataset. Another locus at chr12q24.31 is associated with T2D at suggestive significance level (top SNP rs4758690, P = 4.20 × 10−5) and it is a robust eQTL for the gene, MLXIP (P = 1.10 × 10−14), and is significantly associated with methylation level in MLXIP, the functions of which involves cellular glucose response. Therefore, in this first GWAS of T2D in Jordan subpopulations, we identified novel and unique susceptibility loci which may help inform the genetic underpinnings of T2D in other populations.

scholarly journals Comparison of gene expression in cynomolgus monkeys with preclinical type II diabetes induced by different high energy diets

2019 ◽  
Vol 2 (1) ◽  
pp. 44-50
Author(s):  
Li‐Sha Jin ◽  
Jun‐Hua Rao ◽  
Li‐Biao Zhang ◽  
Fang Ji ◽  
Yan‐Chun Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type Ii Diabetes ◽  
High Energy ◽  
Type Ii ◽  
Cynomolgus Monkeys

Abstract T P240: Sex-specific Differential Gene Expression in a Murine Model of Experimental Intracerebral Hemorrhage

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Sankalp Gokhale ◽  
Dawn Kernagis ◽  
Beilei Lei ◽  
Yi-Ju Li ◽  
David Warner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intracerebral Hemorrhage ◽  
Differential Gene Expression ◽  
Mouse Genome ◽  
Differential Analysis ◽  
Genome Wide ◽  
Collagenase Injection ◽  
Differential Gene ◽  
Males And Females ◽  
Genome Wide Expression

Introduction: Decreased mortality and improved functional outcome in female compared to male mice after experimental intracerebral hemorrhage (ICH) has been demonstrated. We postulate that sex-specific differences in post-ICH gene expression may provide mechanistic insight. Methods: Ten to 12 week old C57/Bl6 male (M) and female in low estrus (LE-F) or high estrous state (HE-F) mice (n=3/group) underwent ICH induction via left intrastriatal collagenase injection. Whole brain samples were collected at baseline, immediately after sham injury and 6 hours after injury. Genome-wide expression profiling was performed with Affymetrix GeneChip Mouse Genome 2.0 to identify genes differentially expressed between baseline and 6 hours in males and females. Probes showing expression levels greater than log2 (10) for all samples were selected for differential analysis. Comparisons were made between baseline and 6-hour time points to determine significant differential gene expression in both sexes. An adjusted p < 0.05 was considered significant. Results: A total of 12136 probes qualified for our filtering criteria, representing 9830 genes. Of the genes tested, 119 in M, 76 in LE-F, and 420 in HE-F were expressed differently at 6 hours as compared to baseline. Of these genes, a total of 37 were shared in M and HE-F groups, 32 in M and LE-F groups, and 42 in HE-F and LE-F groups. Several pathways were identified based on the top list of genes in each group comparison, including coagulation and inflammatory mediator signaling. Conclusions: Sex-specific differential gene expression exists at 6 hours after experimental ICH. Further experiments will be designed to test whether these observed differences in gene expression are associated with outcome after experimental ICH and, thus, may yield novel therapeutic targets for translation into the human disease.

scholarly journals Paradoxically Low Levels of Total and HMW Adiponectin in Relation to Metabolic Parameters in a Tongan Population

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Philip Peake ◽  
Stephen Colagiuri ◽  
Lesley V. Campbell ◽  
Yvonne Shen
Keyword(s):  
Type Ii Diabetes ◽  
Population Survey ◽  
Genetic Variant ◽  
Metabolic Parameters ◽  
Type Ii ◽  
Hmw Adiponectin ◽  
Males And Females ◽  
Low Levels ◽  
Circulating Levels ◽  
Homogenous Population

Aim. Adiponectin has demonstrated anti-inflammatory and insulin sensitising properties, and low circulating levels may be an important risk factor for diabetes. We examined levels of adiponectin and its insulin-sensitising HMW isoform and their relationship with metabolic parameters in Tongans, a population prone to type II diabetes. Methods. Adiponectin and its HMW isoform were quantitated by Elisa in specimens from a randomly recruited, multistage cluster population survey of Tongans and from a group of Caucasians. Anthropometric, clinical, and biochemical data were collected on each subject. Results. Both male and female Tongans had lower levels of total and HMW adiponectin than their Caucasian counterparts. Levels of total and HMW adiponectin were higher in females than males in each group. Adiponectin levels were inversely related to BMI, weight, and HOMA in Tongan males and females, as well as to dyslipidemia in both sexes. Conclusion. Tongans had lower levels of both total and HMW adiponectin than Caucasians population, even after matching Tongans to their Caucasian counterparts based on BMI, age, and sex. These findings may reflect differences in body composition between the populations not adequately assessed by BMI, lifestyle factors, or a genetic variant likely in a genetically homogenous population.

scholarly journals Genetic Determinants of Obesity Heterogeneity in Type II Diabetes

2020 ◽  
Author(s):  
Somayeh Alsadat Hosseini Khorami ◽  
Mohd Sokhini Abd Mutalib ◽  
Mohammad Feili Shiraz ◽  
Joseph Anthony Abdullah ◽  
Zulida Rejali ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Molecular Mechanism ◽  
Type Ii Diabetes ◽  
Insulin Signalling ◽  
Diabetic Group ◽  
Akt Pathway ◽  
Type Ii ◽  
Fasting State ◽  
Significant Difference

Abstract Background: Although obesity is considered as the main cause of Type II diabetes (T2DM), non-obese individuals may still develop T2DM and obese individuals may not. Method: The mRNA expression of insulin signalling components (PI3K/AKT axis) from 100 non-obese and obese participants with insulin sensitivity and insulin resistance states were compared in this study toward the understanding of obesity heterogeneity molecular mechanism. Result: In present study, there was no statistically significant difference in gene expression levels of IRS1 and PTEN between groups, whereas PI3K, AKT2 and GLUT4 genes were expressed at a lower level in obese diabetic group compared to other groups. PDK1 gene was expressed at a higher level in non-obese diabetic group compared to obese diabetic and non-obese non-diabetics groups. No statistically significant difference was identified in gene expression pattern of PI3K/AKT pathway between obese non-diabetics and non-obese non-diabetics. Conclusion: The components of PI3K/AKT pathway which is related to the fasting state, showed reduced expression in obese diabetic group due to the chronic over-nutrition which may induced insensitivity and reduced gene expression. The pathogenesis of insulin resistance in the absence of obesity in non-obese diabetic group could be due to disturbance in another pathway related to the non-fasting state like gluconeogenesis. Therefore, the molecular mechanism of insulin signalling in non-obese diabetic individuals is different from obese diabetics which more investigations are required to study insulin signalling pathways in greater depth, in order to assess nutritional factors contribute to insulin resistance in obese diabetic and non-obese diabetic individuals.

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