Genetic polymorphisms in estrogen receptors and sexual dimorphism in fat redistribution in HIV-infected patients on HAART.
OBJECTIVE
To investigate genetic single nucleotide polymorphisms (SNPs) in estrogen receptor-α (ERα) (ESR1, rs2234693, rs1801132, rs7757956 and rs2813544) and ERβ (ESR2, rs3020450, rs7154455 and rs4986938) genes and relate them to the adverse effects lipodystrophy, dyslipidemia and metabolic syndrome as well as to differences in their prevalence between sexes in HIV-infected individuals on HAART.


METHODS
Cross-sectional study.


METHODS
Blood samples and anthropometric measurements were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas and Rio Grande in Brazil. The SNPs were genotyped by real-time PCR.


RESULTS
The lipodystrophy subtype frequencies in patients of different sexes showed statistically significant differences; the atrophic pattern was more prevalent in men, and the hypertrophic pattern was more prevalent in women. Furthermore, metabolic syndrome prevalence was higher in women than in men. The ESR1 rs2813544 G-allele was associated with higher measurements of several anthropometric variables in women: BMI, total subcutaneous fat and subcutaneous fat of limbs. Additionally, patients who were AA homozygous for ESR2 rs3020450 presented an increased risk for developing lipoatrophy (prevalence ratio 1.37, 95% confidence interval 1.09-1.73, P = 0.007).


CONCLUSIONS
Significant differences in lipodystrophy and metabolic syndrome prevalence were detected between sexes. Moreover, the ESR1 gene (rs2813544) presented significant sex-specific associations with anthropometric variables, and the ESR2 gene (rs3020450) was associated with an increased risk of developing lipoatrophy. Our results suggest that these genes are in part responsible for the sexual dimorphism in fat tissue redistribution and patterns of lipodystrophy.
Programa de Pós-graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil.
Aline S
AS
Gasparotto
Eduardo
E
Sprinz
Rosmeri K
RK
Lazzaretti
Regina
R
Kuhmmer
Jussara M
JM
Silveira
Rossana P
RP
Basso
Cezar A T
CA
Pinheiro
Mariângela F
MF
Silveira
Jorge P
JP
Ribeiro
Vanessa S
VS
Mattevi
D000328:Adult; D000704:Analysis of Variance; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D050218:Body Fat Distribution; D015992:Body Mass Index; D001938:Brazil / Q000453:epidemiology; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000235:genetics* / Q000821:virology; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D024821:Metabolic Syndrome / Q000235:genetics* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D060888:Real-Time Polymerase Chain Reaction; D012737:Sex Factors
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha