Cholesteryl Ester Transfer Protein (CETP) Genetic Variation and Early Onset of Non‐Fatal Myocardial Infarction

Although Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesteryl esters and triglycerides between lipoprotein particles and thus plays a crucial role in reverse cholesterol transport, the association of variations in the CETP gene with acute myocardial infarction (MI) remains unclear. In this study we examined whether common genetic variation in the CETP gene is related to early‐onset non‐fatal MI risk in a population‐based case‐control study from western Washington State. Genotyping for the CETP ?2708 G/A, ?971 A/G, ?629 A/C, Intron‐I TaqI G/A and exon‐14 A/G (I405V) SNPs was performed in 578 cases with first acute non‐fatal MI and in 666 demographically similar controls, free of clinical cardiovascular disease, identified randomly from the community. In‐person interviews and non‐fasting blood specimens provided data on coronary heart disease risk factors. In men, there was little evidence for an association between single SNPs and MI risk, but in women the age‐ and race‐adjusted OR was found to be significant in 4 out of the 5 CETP single variants. Haplotype analysis revealed two haplotypes associated with MI risk among men. As compared to men homozygous for the most common haplotype D (?2708 G, ?971 G, ?629 C, TaqI G and exon‐14 A), the fully‐adjusted multiplicative model identified haplotype G (?2708 G, ?971 A, ?629 A, TaqI G and exon‐14 G) was associated with a 4.0‐6.0‐fold increased risk of MI for each additional copy; [95%CI 2.4–14.8] and haplotype B (?2708 G, ?971 G, ?629 A, TaqI A and exon‐14 A) showed a significant decreased risk for early onset MI [OR = 0.18; 95%CI 0.04 – 0.75]. An evolutionary‐based haplotype analysis indicated that the two haplotypes associated with the MI risk are most evolutionarily divergent from the other haplotypes. Variation at the CETP gene locus is associated with the risk of early‐onset non‐fatal MI. This association was found to be independent of HDL‐C levels. These data and the sex‐specific findings require confirmation in other populations.     

The effect of whole body vibration exposure on muscle or bone morphology and function in older adults: A systematic review of the literature

Context and objective

The aim of this study was to examine the effect of whole body vibration (WBV), a novel exercise modality, on muscle or bone morphology and function in older adults.

Methods

A literature search of published randomised controlled trials (RCTs) was conducted using multiple databases and hand searching for study designs reporting the effects of WBV in older adults on any outcomes related to muscle function, or muscle or bone morphology. Concomitant exercise was only included if the control group performed the same exercise as the active WBV group, but without vibration.

Results

Six RCTs met the inclusion criteria of this review, three reporting measures of muscle only, two assessing bone measures only and one detailing measures of both bone and muscle. Study design varied greatly across the six trials and only six of 35 musculoskeletal outcomes analysed were statistically significant. All statistically significant improvements were of muscle function.

Conclusions

The published literature to date provides only weak support for the efficacy of WBV exposure for muscle function, muscle morphology, or bone architecture in older adults. Irregularities in study design and WBV protocols across the literature and poor quality trials contribute to this inconsistency, revealing the need for more uniformity in future trials. Future research should be more robust in design, include larger cohorts, longer interventions and standardisation of protocols. They should also investigate the optimal dose–response relationships and variation in vibration characteristics, to determine the true efficacy, clinical relevance, and underlying mechanisms of muscle and bone adaptations.     

Gene variants in the NF-KB pathway (NFKB1, NFKBIA, NFKBIZ) and their association with type 2 diabetes and impaired renal function

The NF-kappaB pathway might play a role in the pathogenesis of renal disease and type 2 diabetes (T2DM). Our aim was to determine whether common polymorphisms in NF-kappaB genes were associated with impaired renal function and T2DM in a cohort of healthy elderly individuals. We studied 487 individuals, all Caucasian and aged 65–85?years. A total of 104 (21%) had impaired renal function (estimated glomerular filtration rate, eGFR?<?60) and 146 (30%) were classified as diabetics. The genotypes of 4 common variants were determined through PCR-RFLP or fluorescent capillary electrophoresis.The NFKB1 variants were significantly associated with T2DM: rs7667496 p?=?0.01, OR?=?1.68; and rs28362491 p?=?0.02, OR?=?1.67. They remained significantly associated in a multiple logistic regression with age, gender, hypertension, body mass index, and cholesterol. There was a trend toward the association of these variants with eGFR?<?60. The two NFKB1 variants were in linkage disequilibrium (D′?=??0.86), and homozygous for the two non-risk alleles (rs7667496 CC?+?rs28362491 II), were significantly more common in the non-diabetics (p?=?0.02).In our cohort the NFKB1 variation was an independent risk factor for developing T2DM. Additional studies to confirm this association are of special interest, as well as studies to give a functional explanation to the genetic association.