Fat mass and obesity-associated gene polymorphisms do not affect metabolic response to hormone therapy in healthy postmenopausal women.
OBJECTIVE
To determine whether fat mass and obesity-associated gene polymorphisms rs9939609 T>A and rs8050136 A>C or their haplotypes influence anthropometric and metabolic variables in recently postmenopausal women receiving hormone therapy.


METHODS
In this randomized crossover study carried out in a university clinic, 86 postmenopausal women consulting for symptoms of estrogen deficiency were genotyped by real-time polymerase chain reaction for single nucleotide polymorphisms rs9939609 T>A and rs8050136 A>C of the fat mass and obesity-associated gene. Haplotypes were constructed from the combination of polymorphisms rs9939609 and rs8050136, and their frequencies were inferred using the PHASE 2.1.1 program. Participants were clinically evaluated before and after 6 months of hormone therapy to determine body mass index (current kg/m(2)) and waist circumference, blood pressure, lipid profile (total cholesterol, HDL cholesterol and triglycerides) plasma glucose (oral glucose tolerance test), and insulin. Blood samples were also drawn for ultra sensitive C reactive protein. The lipid accumulation product index was calculated as (waist [cm] - 58) × triglyceride concentration (mmol/L). Non-normally distributed parameters were log10 transformed before statistical analysis. Measurements at baseline and at follow-up were compared with ANOVA for repeated measures. Data were considered significant at P<0.05.


RESULTS
In women with the homozygous polymorphic AA genotype of the single nucleotide polymorphisms rs9939609 and the wild AA genotype of the single nucleotide polymorphisms rs8050136, lipid accumulation product index and ultra sensitive C reactive protein were higher before hormone therapy in comparison with women with other genotypes from the same single nucleotide polymorphisms group. There was no worsening of any of the anthropometric or metabolic variables, and lipid accumulation product index improved slightly after hormone therapy in SNP rs9939609 (P=0.03) and haplotype AAAA. No changes were observed after hormone therapy in SNP rs8050136.


CONCLUSIONS
The presence of fat mass and obesity-associated gene risk variants in healthy early postmenopausal women does not adversely affect their response to hormone therapy.
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
Ramon B
RB
Ramos
Gislaine K
GK
Casanova
Poli M
PM
Spritzer
D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000736:Androstenes / Q000008:administration & dosage; D001823:Body Composition / Q000235:genetics; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D018592:Cross-Over Studies; D004958:Estradiol / Q000008:administration & dosage; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage; D011506:Proteins / Q000235:genetics*; D055105:Waist Circumference
D000736:Androstenes; D008055:Lipids; D011506:Proteins; D011374:Progesterone; D004958:Estradiol; D002097:C-Reactive Protein; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; C035144:drospirenone