OBJECTIVEThis study aims to investigate the correlation between polymorphism of sex hormone-binding globulin (SHBG) Asp327Asn (rs6259) locus and occurrence of hepatocellular carcinoma (HCC).

METHODS621 cases with HCC and 621 cancer-free controls from two hospitals of Guangxi were recruited from January, 2007 to June, 2010. Single nucleotide polymorphisms (SNP) of SHBG Asp327Asn were detected by ABI7500 Fast Real-Time fluorescence quantitative PCR. Multivariate unconditional logistic regression was applied to analyze risk of HCC among different genotypes carriers and their interaction with the exposure factors. The Kaplan-Meier survival analysis was used to detect the relationship between onset age of HCC and genotypes.

RESULTSThe frequencies of Asp/Asp, Asp/Asn and Asn/Asn genotype in case group were 86.31% (536/621), 12.40% (77/621) and 1.29% (8/621), respectively; while those in control group were 81.00% (503/621), 17.39% (108/621) and 1.61% (10/621), respectively. Significant difference in the genotype frequencies distribution was found between case and control groups (χ2=6.465, P<0.05). Compared with those harboring Asp/Asp genotype, multivariate logistic regression analysis revealed that the HCC risk of Asn/Asn+Asp/Asn genotype carriers was significantly decreased (adjusted OR=0.63, 95%CI: 0.40-0.98). Interaction analysis showed that there was interaction between the polymorphisms and two exposure factors, drinking (adjusted OR=3.45, 95%CI: 1.74-6.83) and HBV infection (adjusted OR=40.77, 95%CI: 21.60-76.97). Among those male patients with history of drinking, survival analysis indicated that the mean age of onset of individuals harboring Asp/Asp genotypes ((47.99±0.75) years-old) was 6 years earlier than those with Asn/Asn or Asp/Asn genotypes ((53.68±2.07) years-old) (χ2=6.91, P<0.01).

CONCLUSIONPolymorphism of SHBG (Asp327Asn) may be associated with both the risk of HCC occurrence and onset age of HCC.

Carcinoma, Hepatocellular ; epidemiology ; genetics ; Case-Control Studies ; Female ; Genotype ; Humans ; Liver Neoplasms ; epidemiology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors ; Sex Hormone-Binding Globulin ; genetics

Female ; Humans ; Male ; Diabetes Mellitus, Type 2/genetics* ; Genetic Predisposition to Disease/genetics* ; Postmenopause ; Risk Factors ; Sex Hormone-Binding Globulin/genetics* ; Testosterone

OBJECTIVETo investigate the relationship of (TAAAA)n repeat polymorphism in the promoter of the sex hormone-binding globulin (SHBG) gene and SHBG serum levels to the glucose metabolic status of Chinese polycystic ovary syndrome (PCOS) patients in Shandong province.

METHODSGeneScan method was used to detect and identify (TAAAA)n repeat number (alleles) and genotypes for 156 controls and 157 patients who were divided into normal glucose tolerance without hyperinsulinemia (NIR group) and with hyperinsulinemia (HI group) and abnormal glucose metabolic (AGM) group according to the results of oral glucose test and insulin resistant test; IRMA was used to measure serum SHBG for part of them.

RESULTSFive alleles containing (TAAAA) 6-10 repeats and 14 genotypes including 6/6, 6/7, 6/8, 6/9, 6/10, 7/7, 7/8, 7/9, 7/10, 8/8, 8/9, 8/10, 9/9, 9/10 repeats genotypes were present in the subjects. Genotype distribution of 6/10 repeats genotype is lower in PCOS than that in control, and 8/9 repeats genotype vice versa (P < 0.01); among PCOS subgroups, the eight repeat genotypes in NIR group is more frequent than that in HI group (P < 0.01), and 7/9 genotype distribution in AGM group is higher than that in NIR group and HI group(P < 0.05-0.01). The serum SHBG levels in homozygous genotype groups exhibit a sequence of 8/8 > 9/9 > 6/6, 7/7 repeats and the fall of serum SHBG trend is in reversed relation with the increase in body mass index (BMI), Homa-IR, and blood pressure. Serum SHBG levels in AGM exhibit a sequence of HI group < NIR group < control but show no statistical difference between both groups.

CONCLUSIONThis study reveals that the repeat number, alleles, genotypes and their distributions in Chinese women are very different from these in foreigners. Some special genotypes and low serum SHBG levels may be associated with PCOS and its glucose metabolic status; some special genotypes may influence Chinese serum SHBG and need more studies, but both SHBG gene polymorphism genotype and serum SHBG are not good indicators to find out the PCOS individual at high risk.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Blood Glucose ; metabolism ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Glucose ; metabolism ; Humans ; Polycystic Ovary Syndrome ; blood ; ethnology ; genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Repetitive Sequences, Nucleic Acid ; genetics ; Sex Hormone-Binding Globulin ; genetics ; metabolism