The (TAAAA)n Polymorphism of the SHBG Gene in Men with the Metabolic Syndrome

Abstract

Objective: Low serum Sex Hormone-Binding Globulin (SHBG) has been proposed as an indicator of the Metabolic Syndrome (MS) and cardiovascular disease in men. On the other hand, the (TAAAA)n repeat polymorphism in the SHBG gene has been shown to affect SHBG levels. The possible role of this polymorphism in the MS was examined in the present study.

Design: The study population consisted of 83 men with MS aged 54.9±14.8 years and 166 healthy men of the same age. The diagnosis of MS was based on the criteria proposed by the National Cholesterol Education Program – Third Adult Treatment Panel (NCEP-ATP III). The waist circumference was recorded and blood samples were obtained after overnight fasting for biochemical and hormonal tests. The SHBG(TAAAA)n polymorphism was genotyped in peripheral blood leucocytes.

Results: Genotype analysis for the (TAAAA)n polymorphism of the SHBG gene in the patients and controls identified 6 alleles having 6–11 TAAAA repeats. Patients with MS had more frequently short-allele genotypes (with 6/6, 6/7, 6/8, 7/7, 7/8 or 8/8 tandem repeats) compared to controls (53% vs. 39.8%, p=0.047). In the entire study population, men homozygous for the 6 TAAAA repeat allele had lower SHBG levels (p=0.01) and higher waist circumference (p=0.006) than men heterozygous or non-carriers of this allele.

Conclusion: Short SHBG(TAAAA)n allele genotypes may play a role in the development of the MS. The mechanism of this contribution remains unclear.

Key words

SHBG - polymorphism - metabolic syndrome

References

• 1 Alberti KG, Zimmet P, Shaw J. Metabolic syndrome – a new world-wide definition. A consensus statement from the International Diabetes Federation.  Diabet Med.. 2006;  23 469-480
• 2 Cousin P, Calemard-Michel L, Lejeune H. et al . Influence of SHBG gene pentanucleotide TAAAA repeat and D327N polymorphism on serum sex hormone-binding globulin concentration in hirsute women.  J Clin Endocrinol Metab. 2004;  89 917-924
• 3 Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome.  Lancet. 2005;  365 1415-1428
• 4 Eriksson AL, Lorentzon M, Mellström D. et al . SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density.  J Clin Endocrinol Metab. 2006;  91 5029-5037
• 5 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: . Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).  JAMA. 2001;  285 2486-2497
• 6 Ferk P, Teran N, Gersak K. The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome.  Hum Reprod. 2007;  22 1031-1036
• 7 Freeman MS, Mansfield MW, Barrett JH. et al . Heritability of features of the insulin resistance syndrome in a community-based study of healthy families.  Diabet Med. 2002;  19 994-999
• 8 Groop L. Genetics of the metabolic syndrome.  Br J Nutr. 2000;  83 (Suppl. 1) S39-S48
• 9 Haiman CA, Riley SE, Freedman ML. et al . Common genetic variation in the sex steroid hormone-binding globulin (SHBG) gene and circulating SHBG levels among postmenopausal women: the Multiethnic Cohort.  J Clin Endocrinol Metab. 2005;  90 2198-2204
• 10 Hajamor S, Després JP, Couillard C. et al . Relationship between sex hormone-binding globulin levels and features of the metabolic syndrome.  Metabolism. 2003;  52 724-730
• 11 Hogeveen KN, Talikka M, Hammond GL. Human sex hormone-binding globulin promoter activity is influenced by a (TAAAA)n repeat element within an Alu sequence.  J Biol Chem. 2001;  276 36383-36390
• 12 Poulsen P, Vaag A, Kyvik K. et al . Genetic vs. environmental etiology of the metabolic syndrome among male and female twins.  Diabetologia. 2001;  44 537-543
• 13 Turk A, Kopp P, Colangelo LA. et al . Associations of serum sex hormone-binding globulin (SHBG) with SHBG gene polymorphisms in the CARDIA male hormone study.  Am J Epidemiol. 2008;  167 412-418
• 14 Vanbillemont G, Bogaert V, De Bacquer D. et al . Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men.  Clin Endocrinol. 2009;  70 303-310
• 15 Xita N, Tsatsoulis A, Chatzikyriakidou A. et al . Association of the (TAAAA)n repeat polymorphism in the sex hormone-binding globulin (SHBG) gene with polycystic ovary syndrome and relation to SHBG serum levels.  J Clin Endocrinol Metab. 2003;  88 5976-5980

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