CDK4 IVS4-nt40 AA genotype and obesity-associated tumors/cancer in Italians – a case-control study

Meenakshisundaram, Ramachandran; Gragnoli, Claudia

doi:10.1186/1756-9966-28-42

Cited by 9 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We excluded families with identical twins and siblings with uncertain identical paternity. The Italian family dataset has provided useful genetic information in T2D and associated phenotypes 12 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 .…”

Section: Methodsmentioning

confidence: 99%

T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia

Han

Haas

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

Insomnia increases type-2 diabetes (T2D) risk. The 12q24 locus is linked to T2D, depression, bipolar disorder and anxiety. At the 12q24 locus, the Proteasome-Modulator 9 (PSMD9) single nucleotide polymorphisms (SNPs) rs74421874 [intervening sequence (IVS) 3+nt460-G>A], rs3825172 (IVS3+nt437-C>T) and rs14259 (E197G-A>G) are linked to: T2D, depression, anxiety, maturity-onset-diabetes-of the young 3/MODY3, obesity, waist circumference, hypertension, hypercholesterolemia, T2D-macrovascular disease, T2D-microvascular disease, T2D-neuropathy, T2D-carpal-tunnel syndrome, T2D-nephropathy, T2D-retinopathy and non-diabetic retinopathy. PSMD9 SNP rs1043307/rs14259 (E197G-A>G) plays a role in anti-depressant therapy response, depression and schizophrenia. We aimed at determining PSMD9 rs74421874/rs3825172/rs14259 SNPs potential linkage to primary insomnia and sleep hours in T2D families. We recruited 200 Italian T2D families phenotyping them for primary insomnia and sleep hours per night. PSMD9-T2D-risk SNPs rs74421874/rs3825172 and rs1043307/rs14259 were tested for linkage with insomnia and sleep hours. Non-parametric-linkage analysis, linkage-disequilibrium-model analysis, single-SNP analysis, cluster-based-parametric analysis, quantitative-trait and variant-component analysis were performed using Merlin software. To validate data, 1000 replicates were executed for the significant non-parametric data. PSMD9 rs74421874 (IVS3+nt460-G>A), rs3825172 (IVS3+nt437-C>T) and rs1043307/rs14259 (E197G-A>G) SNPs are linked to insomnia in our Italian families.

show abstract

Section: Methodsmentioning

confidence: 99%

T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia

Han

Haas

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Families with identical twins, siblings with uncertain identical paternity are excluded. This family dataset has provided useful results for gene identification in MODY3, T2D and associated phenotypes (Gragnoli et al, , , , ,, , ; Godart et al, ; Gragnoli, , ; Gragnoli and Cronsell, ,; Meenakshisundaram and Gragnoli, ,; Meenakshisundaram et al, ,).…”

Section: Methodsmentioning

confidence: 99%

Proteasome Modulator 9 Gene SNPs, Responsible for Anti‐Depressant Response, Are in Linkage With Generalized Anxiety Disorder

Gragnoli

2014

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Proteasome modulator 9 (PSMD9) gene single nucleotide polymorphism (SNP) rs1043307/rs2514259 (E197G) is associated with significant clinical response to the anti-depressant desipramine. PSMD9 SNP rs74421874 [intervening sequence (IVS) 3 + nt460 G>A], rs3825172 (IVS3 + nt437 C>T) and rs1043307/rs2514259 (E197G A>G) are all linked to type 2 diabetes (T2D), maturity-onset-diabetes-of the young 3 (MODY3), obesity and waist circumference, hypertension, hypercholesterolemia, T2D-macrovascular and T2D-microvascular disease, T2D-neuropathy, T2D-carpal tunnel syndrome, T2D-nephropathy, T2D-retinopathy, non-diabetic retinopathy and depression. PSMD9 rs149556654 rare SNP (N166S A>G) and the variant S143G A>G also contribute to T2D. PSMD9 is located in the chromosome 12q24 locus, which per se is in linkage with depression, bipolar disorder and anxiety. In the present study, we wanted to determine whether PSMD9 is linked to general anxiety disorder in Italian T2D families. Two-hundred Italian T2D families were phenotyped for generalized anxiety disorder, using the diagnostic criteria of DSM-IV. When the diagnosis was unavailable or unclear, the trait was reported as unknown. The 200 Italians families were tested for the PSMD9 T2D risk SNPs rs74421874 (IVS3 + nt460 G>A), rs3825172 (IVS3 +nt437 T>C) and for the T2D risk and anti-depressant response SNP rs1043307/rs2514259 (E197G A>G) for evidence of linkage with generalized anxiety disorder. Non-parametric linkage analysis was executed via Merlin software. One-thousand simulation tests were performed to exclude results due to random chance. In our study, the PSMD9 gene SNPs rs74421874, rs3825172, and rs1043307/rs2514259 result in linkage to generalized anxiety disorder. This is the first report describing PSMD9 gene SNPs in linkage to generalized anxiety disorder in T2D families.

show abstract

“…Finally, in support of a metabolic function of the cyclin D/cdk4 holoenzyme in metabolism is the finding that some specific polymorphisms in the cdk4 gene could contribute to type II diabetes-associated obesity (Meenakshisundaram and Gragnoli, 2009a). Strikingly, the same cdk4 IVS4-nt40 AA genotype is significantly associated with cancer in obese patients (Meenakshisundaram and Gragnoli, 2009b). In summary, cyclin Ds/cdk4 regulates both cell growth and metabolism, thus integrating both processes in cellular function in normal and in transformed cells.…”

Section: The New Role Of Cell Cycle Regulators: Metabolic Controlmentioning

confidence: 99%

Re-thinking cell cycle regulators: the cross-talk with metabolism

Fajas¹

2013

Front. Oncol.

View full text Add to dashboard Cite

Analysis of genetically engineered mice deficient in cell cycle regulators, including E2F1, cdk4, and pRB, showed that the major phenotypes are metabolic perturbations. These key cell cycle regulators contribute to lipid synthesis, glucose production, insulin secretion, and glycolytic metabolism. It has been shown that deregulation of these pathways can lead to metabolic perturbations and related metabolic diseases, such as obesity and type II diabetes. The cyclin–cdk–Rb–E2F1 pathway regulates adipogenesis in addition to its well-described roles in cell cycle regulation and cancer. It was also shown that E2F1 directly participates in the regulation of pancreatic growth and function. Similarly, cyclin D3, cdk4, and cdk9 are also adipogenic factors with strong effects on whole organism metabolism. These examples support the emerging notion that cell cycle regulatory proteins also modulate metabolic processes. These cell cycle regulators are activated by insulin and glucose, even in non-proliferating cells. Most importantly, these cell cycle regulators trigger the adaptive metabolic switch that normal and cancer cells require in order to proliferate. These changes include increased lipid synthesis, decreased oxidative metabolism, and increased glycolytic metabolism. In summary, these factors are essential regulators of anabolic biosynthetic processes, blocking at the same time oxidative and catabolic pathways, which is reminiscent of cancer cell metabolism.

show abstract

CDK4 IVS4-nt40 AA genotype and obesity-associated tumors/cancer in Italians – a case-control study

Cited by 9 publications

References 16 publications

T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia

T2D and Depression Risk Gene Proteasome Modulator 9 is Linked to Insomnia

Proteasome Modulator 9 Gene SNPs, Responsible for Anti‐Depressant Response, Are in Linkage With Generalized Anxiety Disorder

Re-thinking cell cycle regulators: the cross-talk with metabolism

Contact Info

Product

Resources

About