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Biomedical subjects

Sukhbir Dhamrait

Publications and source records attributed to Sukhbir Dhamrait.

8 recordsLinked to original sources

Does angiotensin-1 converting enzyme genotype influence motor or cognitive development after pre-term birth?

ABSTRACT : BACKGROUND : Raised activity of the renin-angiotensin system (RAS) may both amplify inflammatory and free radical responses and decrease tissue metabolic efficiency and thus enhance cerebral injury in the preterm infant. The angiotensin-converting enzyme (ACE) DD genotype is associated with raised ACE and RAS activity as well as potentially adverse stimuli such as inflammation. The DD genotype has been associated with neurological impairments in the elderly, and thus may be also associated with poorer motor or cognitive development amongst children born preterm prematurely. METHODS : The association of DD genotype with developmental progress amongst 176 Caucasian children born at less than 33 weeks gestation (median birthweight 1475 g, range 645-2480 g; gestation 30 weeks, range 22-32; 108 male) was examined at 2 and 5 1/2 years of age. Measured neuro-cognitive outcomes were cranial ultrasound abnormalities, cerebral palsy, disability, Griffiths Developmental Quotient [DQ] at 2 yrs, and General Cognitive Ability [British Ability Scales-11] and motor performance [ABC Movement], both performed at 5 1/2 yrs. All outcomes were correlated with ACE genotype. RESULTS : The DD genotype was not associated with lower developmental quotients even after accounting for important social variables. CONCLUSION : These data do not support either a role for ACE in the development of cognitive or motor function in surviving infants born preterm or inhibition of ACE as a neuroprotective therapy.

Journal Article↗

Circulating angiotensin converting enzyme activity is correlated with muscle strength.

PURPOSE: The D-variant of the angiotensin-1 converting enzyme (ACE) gene is associated with higher circulating and tissue ACE activity. Some studies have suggested a similar association of genotype with muscle strength or the gain in strength in response to training. This study has assessed the relationship between circulating ACE activity, strength, and the response to training. METHODS: Eighty-one untrained men were tested for quadriceps muscle strength, and 44 of these performed an 8-wk program of dynamic strength training of the quadriceps muscle group. Venous blood was obtained for assessment of circulating ACE activity before and after the training program. ACE genotype was also determined. RESULTS: At baseline, circulating ACE activity was significantly correlated with isometric (r = 0.25-0.29, P < 0.02) and isokinetic (r = 0.38, P < 0.0005) quadriceps muscle strength. ACE genotype also seemed to be related to pretraining muscle strength. However, circulating ACE activity showed no significant association with the 9-14% mean increases of muscle strength in response to the training intervention. ACE genotype also showed no association with the training-induced change in muscle strength. Circulating ACE activity did not change significantly after the training program. CONCLUSIONS: The data support a role for ACE in the regulation of human skeletal muscle strength, but do not confirm a role in altering the response to short-term training.

Adolescent↗

The ACE gene insertion/deletion polymorphism and elite endurance swimming.

Human physical performance is influenced by genetic factors. A variation in the human angiotensin I-converting enzyme (ACE) gene has been identified, in which the insertion (I) variant may be associated with elite endurance performance, and the deletion (D) variant seems overrepresented amongst elite sprinters and short-distance swimmer status. We might thus anticipate I-allele frequency to be elevated amongst swimmers competing over very much greater distances, and have examined this hypothesis. Thirty-five truly elite very-long-distance swimmers were classified as better at 1- to 10-km distances (n=19, SLD group) or those best at 25-km races (n=16, LLD group). Genotype frequencies (II versus ID versus DD) differed between the two groups: 6% versus 47% versus 47% for SLD, and 18.8% versus 75% versus 6.2% for LLD (P=0.01). I-allele frequency was 0.29 for the shorter distance swimmers, and 0.59 for the 25 km group. These data are consistent with an association of ACE I allele with longer distance swimming, and the ACE D allele with swimming shorter distances.

Adult↗

Angiotensin-converting enzyme DD genotype is associated with worse perinatal cardiorespiratory adaptation in preterm infants.

OBJECTIVES: The angiotensin-converting enzyme (ACE) deletion (D) variant is associated with greater ACE activity and perhaps with deleterious cardiorespiratory pathophysiological responses. We determined whether the early health status of the preterm infant was adversely influenced by homozygosity for the D allele (DD genotype) compared with ID or II genotype. Study design Angiotensin-converting enzyme genotype was determined in a cohort of 148 preterm infants born in Bristol, United Kingdom (median gestational age, 31 weeks; range, 28-32). Intensive care data were prospectively obtained. Primary analysis was by Mann-Whitney U and chi(2) tests. RESULTS: Higher oxygen, circulatory support requirements, and base deficit in the first 12 hours after birth were found in infants with DD genotype (minimum inspired oxygen concentration in first 12 hours, median [interquartile range], DD 0.26 [0.21-0.40], ID/II 0.21 [0.21-0.30], P=.028; blood pressure support in first 12 hours, DD 12 [30%], ID/II 15 [14%], P=.039; worse base deficit in first 12 hours, DD 4.8 [7.7 to 0], ID/II 0 [5.3 to 0], P=.020). CONCLUSIONS: Angiotensin-converting enzyme polymorphism has a role in the development of preterm cardiorespiratory disease. The DD genotype, encoding higher angiotensin-converting enzyme activity, may adversely influence the early health status of preterm infants.

Cardiovascular Diseases↗

Is interleukin-6 -174 genotype associated with the development of septicemia in preterm infants?

OBJECTIVE: Systemic infection affects one quarter of preterm infants. Defense from infection is in part mediated by the cytokine interleukin-6 (IL-6). We tested the hypothesis that the IL-6 -174 GG genotype, associated with lower IL-6 response to inflammation, is also associated with the development of septicemia in preterm infants. METHODS: The study group comprised 157 infants who were born at < or =32 weeks. Genotype distribution (34% [54] GG, 46% [72] GC, 20% [31] CC) and C allele frequency (0.43; 95% confidence interval [CI]: 0.37-0.48) were similar to the UK adult population. Among the patients who developed bacterially confirmed septicemia (n = 51 [33%]), there was a significantly higher prevalence of the IL-6 -174 GG genotype than that observed in those who did not develop infection (47% vs 28% for GG: odds ratio [OR]: 2.3; 95% CI: 1.1-4.5). This association remained statistically significant (OR: 2.7; 95% CI: 1.2-6.3) after multiple binary logistic regression adjustment for other significant predictors of the development of septicemia. Late infection alone was similarly associated with GG genotype (septicemia 47% vs no septicemia 29% for GG: OR: 2.2; 95% CI: 1.1-4.3). CONCLUSIONS: Variation in the IL-6 gene seems to influence the defense against bacterial pathogens in the very preterm infant.

Alleles↗