Publication: Postmenopozal Metabolik Sendrom hastalarında seks hormonu bağlayıcı Globulin (SHBG) gen polimorfizmi
Abstract
Metabolik sendrom (MS) postmenopozal kadınlarda sık görülmektedir. Seks hormonu bağlayıcı globulin (SHBG) hormonal dengeyle ilişkili önemli bir biyokimyasal belirteçdir. Bu çalışmada, MS olan ve olmayan posmenopozal kadınlarda iki tane SHBG gen polimorfizmi (rs1799941 ve rs6257) değerlendirdik. Önceki klinik çalışmalarda rs1799941(A/ G) polimorfizmi için G allelinin, rs6257(T/ C) polimorfizmi için T allelinin düşük SHBG düzeyi ile ilişkili olduğu saptanmıştır. Çalışmada NCEP ATP III kriterlerine göre MS tanısı konulan 182 tane postmenopozal kadın ve kontrol grubu olarak MS olmayan zayıf 119 tane postmenopozal kadın dahil edilmiştir. rs1799941(A/ G) ve rs6257(T/ C) polimorfizminin MS kriterleri ve SHBG düzeyiyle ilişkisini değerlendirdik. MS grubunda median SHBG seviyeleri anlamlı derecede düşük saptandı. Median (IQR) SHBG düzeyleri kontrol ve MS grubunda 38(29), 30(23) nmol/ l olarak saptandı (p=0.036). Minör allel sıklığı rs6257(C) ve rs1799941(A) için %19,1 ve %16,6 olarak saptandı. Hardy-Weinberg eşitliğinden sapma görülmedi (rs6257 için p=0,8, rs1799941 için p=0,6). SHBG düzeyleri rs6257 genotipinde benzer olarak saptandı. Ancak, rs1799941 genotipinde SHBG düzeyinde anlamlı farklılık saptandı. MS ve kontrol grubunda rs1799941 (A/ G) polimorfizminin AA+GA ve GG genotipi için Median (IQR) SHBG düzeyleri 44(36), 29(17) ve 56(45), 34(20) nmol/ l olarak saptandı (p=0,031, p=0,005). SHBG gen polimorfizmi ve kardiyovasküler risk faktörleri arasında anlamlı ilişki saptanmıştır. MS grubunda rs1799941(A/ G) polimorfizminde AA+AG ve GG genotipleri için sistolik ve diyastolik kan basıncı median (IQR) değerleri 142(15), 145(18) mmHg ve 80(11), 85(11) mmHg olarak saptandı (p=0,012, p=0,040). Gruplar arasında GG alleli ile AG+AA allelleri, BMI ve bel çevresi (WC) açısından karşılaştırıldı. BMI ve WC düzeyleri 31(8), 33(7) kg/ m2 ve 96(14), 102(17) cm olarak saptandı (p=0,29, p=0,03). 1799941(A/ G) SHBG gen polimorfizminde fonksiyonel özellik kazancıyla ilişkili olarak SHBG düzeyinde artış olmaktadır. Sonuç olarak postmenopozal kadınlarda GG genotipi, obezite, yüksek kan basıncı ve metabolik sendroma genetik yatkınlığı belirlemektedir. Metabolik Sendrom, SHBG, Gen Polimorfizmi iv
Metabolic syndrome (MS) is common among postmenopausal women. Sex hormone binding globulin (SHBG) is an important biomarker related to hormonal balance. In this study, we examined two genetic polymorphisms of SHBG gene (rs1799941 and rs6257) among postmenopausal women with and without MS. Prior clinical studies have reported that G allele of the rs1799941 and T allele of rs6257 polymorphisms are associated with low SHBG levels. The study population consisted of 182 postmenopausal women with MS according to NCEP ATP III criteria and 119 lean postmenopausal women without MS were selected as controls. We analysed frequency of A/ G alleles of rs1799941 and T/ C alleles of rs6257 polymorphisms to study the associations gene polymorphisms with MS risk components and SHBG levels. Median (IQR) levels of SHBG were significantly lower among MS subjects. Median (IQR) levels of SHBG were 38(29), 30(23) nmol/ l for lean and MS subjects respectively (p=0.036). The minor allelic frequencies for rs6257(C) and rs1799941(A) were %19,1 and %16,6, respectively. There was no evidence for deviation from the Hardy Weinberg Equilibrium (rs6257, p=0.8, rs1799941, p=0.6). SHBG levels were similar among rs6257 genotypes. However, significant differences were noted in SHBG levels among rs1799941 genotypes. Median (IQR) SHBG levels were 44(36), 29(17) and 56(45), 34(20) nmol/ l for AA+GA and GG genotypes of rs1799941(A/ G) polymorphisms for MS and lean subjects respectively (p=0.031, p=0,005). There were significant associations between cardiovascular risk variables and SHBG gene polymorphisms. For instance, among subjects with MS, systolic and diastolic blood pressure median (IQR) levels were 142(15), 145(18) mmHg and 80(11), 85(11) mmHg for AA+GA and GG genotypes of rs1799941 (A/ G) polymorphism, respectively (p=0.012, P=0,040). We compared BMI and waist circumference (WC) between subjects with GG allele versus AG+AA of rs1799941 polymorphisms. BMI and WC levels were 31(8), 33(7) kg/ m2 and 96(14), 102(17) cm (p=0.029, p=0.003). 1799941(G/ A) SHBG gene polymorphisms associate with gain of function characteristics to increase SHBG levels. Hance 1799941 GG genotype may determine postmenopausal women with genetic predisposition to obesity, high blood pressure and metabolic syndrome. KEY WORDS, Metabolic syndrome, SHBG, gene polymorphisms
Metabolic syndrome (MS) is common among postmenopausal women. Sex hormone binding globulin (SHBG) is an important biomarker related to hormonal balance. In this study, we examined two genetic polymorphisms of SHBG gene (rs1799941 and rs6257) among postmenopausal women with and without MS. Prior clinical studies have reported that G allele of the rs1799941 and T allele of rs6257 polymorphisms are associated with low SHBG levels. The study population consisted of 182 postmenopausal women with MS according to NCEP ATP III criteria and 119 lean postmenopausal women without MS were selected as controls. We analysed frequency of A/ G alleles of rs1799941 and T/ C alleles of rs6257 polymorphisms to study the associations gene polymorphisms with MS risk components and SHBG levels. Median (IQR) levels of SHBG were significantly lower among MS subjects. Median (IQR) levels of SHBG were 38(29), 30(23) nmol/ l for lean and MS subjects respectively (p=0.036). The minor allelic frequencies for rs6257(C) and rs1799941(A) were %19,1 and %16,6, respectively. There was no evidence for deviation from the Hardy Weinberg Equilibrium (rs6257, p=0.8, rs1799941, p=0.6). SHBG levels were similar among rs6257 genotypes. However, significant differences were noted in SHBG levels among rs1799941 genotypes. Median (IQR) SHBG levels were 44(36), 29(17) and 56(45), 34(20) nmol/ l for AA+GA and GG genotypes of rs1799941(A/ G) polymorphisms for MS and lean subjects respectively (p=0.031, p=0,005). There were significant associations between cardiovascular risk variables and SHBG gene polymorphisms. For instance, among subjects with MS, systolic and diastolic blood pressure median (IQR) levels were 142(15), 145(18) mmHg and 80(11), 85(11) mmHg for AA+GA and GG genotypes of rs1799941 (A/ G) polymorphism, respectively (p=0.012, P=0,040). We compared BMI and waist circumference (WC) between subjects with GG allele versus AG+AA of rs1799941 polymorphisms. BMI and WC levels were 31(8), 33(7) kg/ m2 and 96(14), 102(17) cm (p=0.029, p=0.003). 1799941(G/ A) SHBG gene polymorphisms associate with gain of function characteristics to increase SHBG levels. Hance 1799941 GG genotype may determine postmenopausal women with genetic predisposition to obesity, high blood pressure and metabolic syndrome. KEY WORDS, Metabolic syndrome, SHBG, gene polymorphisms