Maternal leptin receptor gene variant Gln223Arg is not associated with variation in birth weight or maternal body mass index in UK and South Asian populations.

BACKGROUND: Leptin is an adipocyte secreted hormone involved in regulation of body weight and metabolism in man. Placenta leptin levels correlate positively with birth weight. It is therefore possible that variation in the leptin receptor gene (LEPR) may contribute to obesity and influence birth weight. OBJECTIVE: This study investigates the influence of the leptin receptor gene variant Gln223Arg (A-->G, 668), on maternal body mass index (BMI), foetal gestational length and birth weight in a cohort of 455 healthy pregnant women of Asian Indian (India, Bangladesh, Pakistan) and UK/Irish origin. RESULTS: Maternal genotype distributions did not differ from those expected under Hardy-Weinberg equilibrium conditions in either population of origin. Maternal genotype for the Gln223Arg leptin receptor gene polymorphism showed no significant association with foetal birth weight (adjusted for gestational length) or with maternal BMI during first trimester (adjusted for age) in either population group. CONCLUSION: These results suggest that the Gln223Arg variant in the maternal leptin receptor gene does not explain the association between placental leptin levels and birth weight, and is not associated with variation in maternal BMI in early pregnancy in our sample.

Association of the TNF-alpha-308 (G-->A) polymorphism with self-reported history of childhood asthma.

Asthma is a complex disease involving genetic and environmental aetiology. The tumour necrosis factor-alpha (TNF-alpha) and angiotensin-converting enzyme (ACE) genes have been implicated in asthma pathogenesis. This study investigated the association of a G-308A variant of TNF-alpha and an insertion/deletion (I/D) variant of ACE with a self-reported history of childhood asthma, in two population groups. At Northwick Park Hospital, London, 1,811 pregnant women attending for antenatal care were recruited. Participants with a self-reported history of childhood asthma, determined by a researcher-administered questionnaire, and controls with no personal or family history of asthma, of UK/Irish (cases n=20; controls n=416) and South Asian (cases n=6; controls n=275) origin were used in this study. Participants were genotyped for the TNF-alpha-308 and ACE I/D variants by a PCR-RFLP and PCR approach. The TNF-alpha-308 allele 2 (-308A) was significantly associated with self-reported childhood asthma in the UK/Irish (Odds ratios (OR): 2.6; 95% confidence intervals (CI): 1.1-6.2; P=0.03) but not in the South Asian population. The ACE DD genotype was not associated with childhood asthma in either population group. Gametic phase disequilibrium between the TNF-alpha-308 and ACE I/D variants was significantly different from zero in UK/Irish cases (delta=0.09; P=0.034). The TNF-alpha308 allele 2 or a linked major histocompatibility complex (MHC) variant may be a genetic risk factor for childhood asthma in the UK/Irish sample.