Disease relevance of GGN

• MATERIALS AND METHODS: The SRD5A2 polymorphisms A49T, V89L and R227Q, the androgen receptor CAG and GGN repeats and sex hormone status was investigated in men with prostate cancer (CaP) (n=89), benign prostate hyperplasia (n=45) and healthy military conscripts (n=223) [1].
• Hence, we performed a case-control study to assess whether GGN repeats independently or in combination with CAG repeats were associated with prostate cancer risk in South Indian men [2].
• MEASUREMENTS: Genotyping the GGN and CAG repeats of the AR gene, and measuring body weight, height and waist and hip circumferences [3].
• OBJECTIVE: To examine the relationship between GGN and CAG trinucleotide repeat polymorphisms in the androgen receptor (AR) gene and indices of obesity in older Caucasian adults [3].
• Median GGN lengths were significantly higher (24 vs. 23) among both subjects with cryptorchidism, compared with controls (P = 0.001), and those with penile hypospadias, compared with either controls (P = 0.003) or glanular and penoscrotal hypospadias combined (P = 0.018) [4].

High impact information on GGN

• The investigation of a large number of genetic variants covering the AR locus suggests that a polyglycine-encoding GGN repeat in exon 1 is a plausible candidate for conferring the functional effect [5].
• More than 72% of the subjects had a GGN repeat length of 23, and those with a GGN repeat length shorter than 23 had a 12% increased risk of prostate cancer (95% confidence interval, 0.71-1.78), compared with those with > or = 23 GGN repeats [6].
• For the GGN tract (GGT3GGG1GGT2GGCn), based on the sequencing results from 481 samples, we are the first to show that although GGC regions in the polyglycine tract are highly variable, there are no mutations or polymorphisms in the GGT and GGG regions [6].
• A mitochondrion-encoded tRNA(Gly) and at least one nucleus-encoded tRNA(Gly) coexist in the mitochondria of these plants, and both are required to allow translation of all four GGN glycine codons [7].
• Our findings indicate an association between GGN length and the risk of cryptorchidism and penile hypospadias, both conditions considered consequences of low androgenicity [4].

Chemical compound and disease context of GGN

• Genomic DNA from 190 prostate cancer patients and 304 healthy controls was used for direct sequencing to evaluate the relationship of CAG and GGN (polyglycine) repeat length in the AR gene [6].

Biological context of GGN

• Our findings indicate that point mutations in the GGN repeat are frequently found in the general male population (1.3%; 95% CI: 0.3-3.9%), but are usually not associated with profound changes in the male phenotype [8].
• However, when CAG repeats of our earlier study was combined with the GGN repeat data, the cases exhibited significantly higher frequency of the haplotypes CAG </=19/GGN </=21 (OR-5.2 at 95% CI-2.17-12.48, P < 0.001) and CAG </=19/GGN > 21(OR-6.9 at 95%CI-2.85-17.01, P < 0.001) compared to the controls [2].
• The ethnic variation in the GGN and CAG microsatellites of the androgen receptor (AR) gene suggests their role in the substantial racial difference in prostate cancer risk [2].
• In univariate survival analysis, patients with short alleles of both repeats (SS-CAG and SS-GGN genotypes simultaneously) had a lower risk of cancer-specific death (p = 0.032, mean follow-up: 63 months) [9].
• The length of the CAG/GGN repeat segment was evaluated by using polymerase chain reaction (PCR) sequencing in exon 1 and PCR-single-strand conformation polymorphism (PCR-SSCP) in exons 2-8 [10].

Anatomical context of GGN

• CONCLUSIONS: Short GGN repeats seem to be associated with decreased semen volume, possibly due to suboptimal AR activity [11].
• The lengths of the androgen receptor (AR) function modulating CAG and GGN repeats in leukocyte DNA were also analysed [12].

Associations of GGN with chemical compounds

• Hence, codon-usage variants of the GGN tract may be used to seek associations with particular diseases, as diagnostic aids in families with androgen insensitivity whose AR mutations have not yet been identified, or as internal controls for observations on intergenerational contractions or expansions of the (CAG)nCAA tract in a given hAR allele [13].
• Two polymorphic trinucleotide repeats of human androgen receptor gene (hAR), CAG and GGN which encode glutamine and glycine, have been shown to be associated with human diseases [14].
• Peripheral infusions of Intralipid and heparin increased arterial plasma NEFA concentrations equally in NEFA + GGN and NEFA + HG and did not change in other protocols [15].
• Additionally, hyperglycemic (HG), hyperglycemic-hyperlipidemic (NEFA + HG), and glycerol plus glucagon (GLYC + GGN) controls were studied [15].
• The glycoconjugates, detected by peanut agglutinin (PNA) which recognizes the disaccharide galactose beta(1-3)N- acetylgalactosamine (GGN), were decreased in the serum of 78.1% of ALS patients, while in CSF they were increased in 54.7% of these cases [16].

Regulatory relationships of GGN

• Because polymorphic CAG and GGN segments regulate AR function, we investigated whether there was any association between these polymorphisms and mentioned malformations [4].

Other interactions of GGN

• Androgen receptor gene GGN repeat length and reproductive characteristics in young Swedish men [11].
• The single-stranded DNA and RNA binding protein, Puralpha, has recently received special attention as this protein, by associating with the specific nucleotide sequence (GGN repeats) and/or several important cellular and viral proteins regulates crucial biological events such as transcription, replication, and cell proliferation [17].

Analytical, diagnostic and therapeutic context of GGN

• Men with GGN<23, exposed to maternal smoking during pregnancy, had higher body mass index compared to men with other GGN lengths, no matter whether their mother had smoked or not during pregnancy (mean difference 4.8 kg/m2, P<0.001) [11].
• Using PCR, the region surrounding the GGN repeat was amplified [18].

References