Body mass index but not a polymorphism of the interleukin-1 receptor antagonist (IL-1 RA) gene is associated with age at natural menopause.
BACKGROUND
A genetic component of the onset of menopause has been described and several candidate genes have been identified. We hypothesized that carriage of a polymorphism of the interleukin-1 receptor antagonist gene (IL-1 RA) is associated with an early age at menopause.


METHODS
In a prospective cohort study, 90 consecutive postmenopausal Caucasian women were genotyped by PCR for the presence of an 86-base pair tandem repeat polymorphism in intron 2 of IL-1 RA.


RESULTS
We found that 36/90 (40%) women were homozygous for the wild-type allele 1 and 49/90 (54%) women were heterozygous for any of the variant alleles (1/2 [n = 44], 1/3 [n = 3], 2/3 [n = 2]). Two women (2%) were homozygous carriers of the variant allele 2. The wild-type allele 1 was identified on 119 of 180 chromosomes for an allele frequency of 0.66. The polymorphic alleles 2 and 3 were present on 56 and 5 chromosomes, respectively (allele frequencies 0.31 and 0.03, respectively). No correlation between the IL-1 RA genotype and the age at menarche and menopause, the length of the reproductive period, and the number of deliveries and miscarriages was ascertained. As to allele frequencies, homozygous and heterozygous carriers of the variant allele 2 had a median age at menopause of 50 (range 40-48) years, compared to 49.5 (range 39-56) years for women with no allele 2 (p value 0.41). Women with at least one allele 2 had a median age at menarche of 13 (range 10-16) years, compared to 13 (range 10-17) years for women with no allele 2 (p value 0.1). Decreasing body mass index, but not smoking, was correlated with an increasing age at natural menopause (r = -0.23, p = 0.04).


CONCLUSIONS
Our preliminary data suggest that an 86-base pair tandem repeat polymorphism in intron 2 of IL-1 RA does not modulate the onset and cessation of menses in this cohort of Caucasian women.
Riener
Eva-Katrin
EK
Department of Obstetrics and Gynecology, University of Freiburg Medical School, Freiburg, Germany.
Keck
Christoph
C
Worda
Christof
C
Hefler
Lukas A
LA
Tempfer
Clemens B
CB
D000328:Adult; D000367:Age Factors; D000483:Alleles; D000704:Analysis of Variance; D001483:Base Sequence; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008572:Menarche / Q000502:physiology; D008593:Menopause / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012795:Sialoglycoproteins / Q000235:genetics*; D018709:Statistics, Nonparametric
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins