Sex- and Obesity-specific Association of Aromatase (CYP19A1) Gene Variant with Apolipoprotein B and Hypertension

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• 作者：Neslihan Coban^a ; ^{neslic@istanbul.edu.tr" class="auth_mail" title="E-mail the corresponding author} ; Altan Onat^b ; Filiz Guclu-Geyik^a ; Gunay Can^c ; Nihan Erginel-Unaltuna^a
• 关键词：Apolipoprotein B ; CYP19A1 polymorphism ; Insulin resistance ; Sex disparity ; TARF study
• 刊名：Archives of Medical Research
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：46
• 期：7
• 页码：564-571
• 全文大小：256 K

文摘

Gender differences in cardiovascular disease risk have been attributed to sex hormones. The CYP19A1 protein (aromatase) plays a critical role in estrogen biosynthesis and thus affects body fat distribution and regulation. We examined the relationship between polymorphism of the CYP19A1 gene and lipoproteins, body mass index (BMI), insulin levels and HOMA index.

Methods

Randomly selected 2250 Turkish adults (aged 49.7 ± 11.9 years; 48.6% males) were genotyped for CYP19A1 rs10046 polymorphism using hybridization probes in Real-Time PCR LC480 device.

Results

Distribution of the CYP19A1 rs10046 polymorphism was 28% (n = 630), 48.3 % (n = 1085) and 23.7% (n = 535) for the CC, CT and TT genotypes, respectively, and the T allele frequency was 0.48. In relation to apolipoprotein (apo)B levels, C homozygosity was associated with higher apoB in non-obese females, contrasting to being so in obese males only, and further in postmenopausal females. CC genotype in females was associated in linear regression analysis by 7.2 ± 3.3 mg/dL higher apoB than CT + TT genotypes, independent of age and BMI. Among premenopausal females, insulin levels (p = 0.007), BMI (p = 0.05) and HOMA index (p = 0.034) were higher in C homozygotes than in T-allele carriers. However, CYP19A1 TT genotype contributed to hypertension at an OR 1.80 (95% CI 1.12–2.91), independently of age, BMI and other confounders, in males alone.

Conclusion

The CYP19A1 rs10046 polymorphism is associated with cardiovascular risk factors such as circulating apoB, insulin resistance and hypertension in a sex- and obesity-specific manner.