Null mutation in human ciliary neurotrophic factor gene confers higher body mass index in males.
Ciliary neurotrophic factor (CNTF) administration reduces weight in leptin-resistant mice via the signalling pathway normally activated by leptin. A G>A null mutation in the CNTF gene results in complete absence of protein. We hypothesised that absence of CNTF could lead to diminished initiation of anorectic pathways, with consequent increase in body mass. In 575 Caucasian men aged 59-73 years, the A/A genotype (frequency 1.9%) was associated with a 10 kg increase in weight (P=0.03, 2 df) and 3 kg/m(2) greater BMI (P=0.02, 2 df). There was no effect in women. The CNTF G>A null mutation therefore confers a moderate effect on obesity in males of A/A genotype, who represent 1% of the general population.
O'Dell
Sandra D
SD
Division of Human Genetics, University of Southampton School of Medicine, Duthie Building (MP 808), Southampton General Hospital, Tremona Road, Southampton S016 6YD, UK. S.D.O'Dell@soton.ac.uk
Syddall
Holly E
HE
Sayer
Avan Aihie
AA
Cooper
Cyrus
C
Fall
Caroline H D
CH
Dennison
Elaine M
EM
Phillips
David I W
DI
Gaunt
Tom R
TR
Briggs
Patricia J
PJ
Day
Ian N M
IN
D000368:Aged; D015992:Body Mass Index; D016009:Chi-Square Distribution; D020934:Ciliary Neurotrophic Factor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
D020934:Ciliary Neurotrophic Factor