The influence of Nos3 polymorphisms on age at menarche and natural menopause.
OBJECTIVE
Deficiency of the gene encoding endothelial nitric oxide synthase, i.e. Nos3, has been reported to be associated with late menarche, reduced ovulation rates, fewer deliveries, and earlier onset of menopause in a mouse model.


METHODS
We assessed the Glu298Asp and the T-786C polymorphisms of Nos3 in 87 consecutive healthy postmenopausal women by pyro- and capillary-sequencing, respectively. Results were correlated with age at menarche and natural menopause, number of miscarriages and live births, as well as body mass index (BMI) and smoking habits.


RESULTS
Allelic frequencies of the Glu298Asp polymorphism of Nos3 were 121 (69.5%) and 53 (30.5%) for the wild-type G allele and the mutant T allele, respectively. Forty-one women (47.1%) were homozygote wild-type (G/G), 39 (44.9%) were heterozygote (G/T), and 7 (8.0%) were homozygote mutant (T/T). Allelic frequencies of the T-786C polymorphism of Nos3 were 105 (60.6%) and 69 (39.4%) for the wild-type T allele and the mutant C allele, respectively. Thirty-three women (38.0%) were homozygote wild-type (T/T), 39 (45.1%) were heterozygote (T/C), and 15 (16.9%) were homozygote mutant (C/C). Presence of at least one mutant allele of the Glu298Asp or the T-786C polymorphisms of Nos3 were not associated with age at menarche, natural menopause, and number of miscarriages and deliveries. BMI above 27 kg/m2 and smoking were associated with earlier onset of natural menopause (47.8 years versus 50.2 years (P = 0.01) and 46.8 years versus 49.8 years (p = 0.02)).


CONCLUSIONS
Our data show that smoking and increased BMI, but not Glu298Asp or the T-786C polymorphisms of Nos3, are associated with an early onset of natural menopause.
Department of Obstetrics & Gynecology, University of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria. christof.worda@akh-wein.ac.at
Christof
C
Worda
Katharina
K
Walch
Michael
M
Sator
Wolfgang
W
Eppel
Clemens B
CB
Tempfer
Christian
C
Schneeberger
Johannes C
JC
Huber
Lukas A
LA
Hefler
D000367:Age Factors; D000375:Aging / Q000235:genetics*; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008572:Menarche / Q000235:genetics*; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic / Q000502:physiology*; D012044:Regression Analysis; D012907:Smoking / Q000503:physiopathology
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III