The −597 G→A and −174 G→C Polymorphisms in the Promoter of the IL-6 Gene Are Associated with Hyperandrogenism

Abstract

To evaluate whether genetic variability at the IL-6 gene (IL-6) is associated with hyperandrogenism, we studied four common polymorphisms in the IL-6 promoter (-597G-->A, -572G--> C, -373A(n)T(n), -174G-->C) in 85 hyperandrogenic patients and 25 healthy women. We found 5 different haplotypes when considering the 3 biallelic polymorphisms at positions -597, -572, and -174 of IL-6 (relative frequencies in parentheses): GGG (0.505), AGC (0.377), GGC (0.059), GCG (0.055), and GCC (0.005). The frequencies of the GGG haplotype were 0.559 in patients and 0.320 in controls, whereas those of the AGC haplotype were 0.318 in patients and 0.580 in controls (chi(2) = 12.145; P < 0.02). The -597G-->A and -174G-->C polymorphisms were in linkage disequilibrium (chi(2) = 152.220; P < 0.00001), and were associated with patient or control status. -597G and -174G alleles were more frequent in patients in homozygosity or considering subjects homozygous and heterozygous for G alleles as a whole (P < 0.05 for all analyses). In healthy women G alleles at -597 and -174 were associated with statistically significant higher circulating levels of IL-6 and basal cortisol, 11-deoxycortisol, and 17-hydroxyprogesterone and a tendency (P < 0.10) for higher total T concentrations compared with -597A and -174C alleles. On the contrary, neither the -572G-->C nor the -373A(n)T(n) polymorphism was related to hyperandrogenism or influenced any clinical or biochemical variable. In conclusion, our present results suggest that the -597G-->A and -174G-->C polymorphisms in IL-6 are involved in the pathogenesis of hyperandrogenic disorders.

Genetic Basis of Metabolic Abnormalities in Polycystic Ovary Syndrome

“…[103] We recently found that Therefore, it could be hypothesized that proinflammatory gecommon G alleles of the -597G/A and -74G/C IL6 gene notypes and phenotypes might also be associated with PCOS and polymorphisms, which are in linkage disequilibrium, are assohyperandrogenism, considering that insulin resistance is an inteciated with hyperandrogenism in a study involving 85 patients and gral part of PCOS, and that obesity, type 2 diabetes, and an 25 healthy women from Spain. [100] Moreover, when studying increased cardiovascular risk profile, are frequent findings in controls alone, carriers of G alleles presented higher serum IL-6, women presenting with PCOS.…”

Hyperandrogenism, Insulin Resistance and Hyperinsulinemia as Cardiovascular Risk Factors in Diabetes Mellitus

“…C-reactive protein may be increased PCOS women, although a recent study from our group suggests that obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in these women [85]. However, we have described that certain proinflammatory genotypes are associated with PCOS and hyperandrogenism, suggesting that chronic inflammation contributes to the development of these disorders [86][87][88][89]. PCOS has also been associated with impaired fibrinolysis [82] and increased homocysteine levels [90].…”

Impact of host gene polymorphisms on susceptibility to chronic hepatitis B virus infection

“…While it seems that the CC genotype is an important protective factor for HBV-related cirrhosis development (Saxena et al, 2014d). Although, the studies in Spanish population reported that IL-6-597G allele is related to the increased levels of IL-6 in serum, but there was no significant relationship between IL-6-572 and IL-6-597 genotypes and IL-6 levels (Villuendas et al, 2002).…”