Estimation of the appendicular skeletal muscle mass and phase angle cut-off values from a young Turkish reference population using multifrequency bioelectrical impedance analysis.

OBJECTIVE: Population-specific muscle mass cut-off values are recommended for the diagnosis of sarcopenia. In this study, we aimed to determine the appendicular muscle mass index (ASMI) and phase angle (PA) cut-off values for the Turkish population using multi-frequency bioelectrical impedance analysis (mBIA). PATIENTS AND METHODS: A total of 250 healthy volunteers aged 18-40 years were included in the study between September 2020 and December 2021. PA was measured by mBIA, and appendicular skeletal muscle mass (ASM) was calculated by the Sergi formula using the resistance and reactance measurements from mBIA. ASMI was calculated as ASM (kg)/(height in meters)2. Two standard deviations (SD) below the mean values were accepted as cut-off points. RESULTS: 134 women and 116 men were included in the study (26.0±5.6 years). The ASMI cut-offs for men and women were 5.86 and 4.36 kg/m2, respectively. The PA cut-offs were 5.66° in men and 4.38° in women. CONCLUSIONS: The present study reported the ASMI and PA cut-off values specific to the Turkish population using the Sergi formula, which was suggested by the European Working Group on Sarcopenia in Older People (EWGSOP).

Interethnic variation in genetic risk factors for vascular disease

Genetic predisposition to vascular disease has important implications for population screening and prevention. The most common hereditary cause of venous thrombosis is resistance to activated protein C caused by the G1691A point mutation in exon 10 of the factor V gene (1q21-25) which leads to the substitution of glutamine for arginine (factor V Leiden). A thermolabile variant of 5, 10-methylenetetrahydrofolate reductase (MTHFR) caused by the C677T mutation of the MTHFR gene (1p36.3) which substitutes valine for alanine is associated with the vascular disease risk factor hyperhomocysteinaemia. The possibility that these mutations may predispose individuals of African-American origin to thrombosis was investigated in 9 patients (6 male, 3 female) with sickle cell anaemia who had experienced a thrombotic episode. The frequency of the MTHFR C677T mutation was also determined in unrelated subjects from six different populations: African-Caribbean (50), Oriental (47), Asian Indian (21), Middle Eastern (24), Meditteranean (50) and Northen European (61). The MTHFR and factor gene regions of interest were amplified by the polymerase chain reaction method. Factor V Leiden was screened for by single strand conformation polymorphism analysis and the MTHFR C 677T mutation by Hinf 1 restriction. All patients were homozygous normal (G/G) for the factor V allele. This is consistent with population studies which failed to identify factor V Leiden in normal subjects of Sub-Saharan African populations and found a low frequency (0.65 percent in Black Americans. By contrasts, factor V Leiden was found to be most prevalent in European populations (from 1.4 percent in Finland to 7 percent in Greece). One patient was heterozygous (C/T) and 8 homozygous normal (C/C) for the MTHFR mutation. Population studies revealed the observed frequency of the mutant allele (T) to be lowest in African-Caribbean subjects (9 percent) of whom none were homozygous and only 18 percent heterozygous. The frequency was highest in the Meditteranean population (42 percent), followed by Middle Eastern (38 percent), Northern European (30 percent), Asian Indian (21 percent) and Oriental (19 percent). No deviation from Hardy-Weinberg equilibrium was detected. The proportion of subjects homozygous for the mutation (T/T) was 18 percent Meditteranean, 17 percent Middle East, 10 percent Northern European and Asian Indian and 2 percent Oriental. (AU)

The molecular basis for genetic variation in fetal haemoglobin level in sickle cell anaemia

Raised fetal haemoglobin levels ameliorate the clinical severity of sickle cell anaemia. This provides a rationale for therapy and signals the need to elucidate the molecular basis for the variability of HbF level in sickle cell anaemia. Polymorphism within regulatory sites of the globin locus alter the affinity with which transcription factors bind their cogante recognition sites thereby modulating gene expression. A novel chromosomal haplotype utilising polymorphic variation within two enhancers hypersensitive site 2 (HS2) of the locus control region and the pre g y framework and the silencer protein BP1 binding site that spans a 53 kb interval of the globin locus was determined in 205 patients with sickle cell anaemia from the UK and Jamaica. Multiplexed polymerase chain reactions developed to facilitate rapid analysis of polymorphisms within each site allowed individual haplotype construction in a single lane of a single strand conformation polymorphism (SSCP) electrophoresis gel. SSCP banding patterns for the combined polymorphic sites were confirmed as unique chromosomal haplotypes by DNA sequence anaylsis. Three hundred and ten chromosomes with sequence TA7 N 12 TA8, GA and AT(AT)8T4 were designated class 1. Twenty-five class II with sequence TA8 N10 TA11, GG, AC(AT)6T9; 17 class III with TA9 N10 TA10, AG, AC(AT)8T4; 7 class IV with TA10 N10 TA12, AG, AC(AT)9T5 and 13 class Ia haplotype with sequence TA9 N10 TA10, GA, AT(AT)8T4 were identified. The proportion of class I chromosomes in both groups (159/210 UK; 151/200 Jamaican) is identical, however, significantly more chromosomes with sub-classes I and II are present among the Jamaican sample. There is incomplete association between the functional haplotype classes defined and conventional haplotypes based on restriction fragment length polymorphisms. The level of Hbf is significantly higher in patients with functional haplotype classes III and IV compared to those with classes I and II. Both high HbF haplotypes share a high affinity binding motif for the transcription factor GATA-1. This novel approach allows the combined effets of genetic variation in regulatory sequences within the globin locus on HbF level to be defined. (AU)