Dataset Information

The genetics of POAG in black South Africans: a candidate gene association study.

ABSTRACT: Multiple loci have been associated with either primary open angle glaucoma (POAG) or heritable ocular quantitative traits associated with this condition. This study examined the association of these loci with POAG, with central corneal thickness (CCT), vertical cup-to-disc ratio (VCDR) and with diabetes mellitus in a group of black South Africans (215 POAG cases and 214 controls). The population was homogeneous and distinct from other African and European populations. Single SNPs in the MYOC, COL8A2, COL1A1 and ZNF469 gene regions showed marginal associations with POAG. No association with POAG was identified with tagging SNPs in TMCO1, CAV1/CAV2, CYP1B1, COL1A2, COL5A1, CDKN2B/CDKN2BAS-1, SIX1/SIX6 or the chromosome 2p16 regions and there were no associations with CCT or VCDR. However, SNP rs12522383 in WDR36 was associated with diabetes mellitus (p = 0.00008). This first POAG genetic association study in black South Africans has therefore identified associations that require additional investigation in this and other populations to determine their significance. This highlights the need for larger studies in this population if we are to achieve the goal of facilitating early POAG detection and ultimately preventing irreversible blindness from this condition.

SUBMITTER: Williams SE

PROVIDER: S-EPMC4323640 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The genetics of POAG in black South Africans: a candidate gene association study.

Williams Susan E I SE Carmichael Trevor R TR Allingham R Rand RR Hauser Michael M Ramsay Michele M

Scientific reports 20150211

Multiple loci have been associated with either primary open angle glaucoma (POAG) or heritable ocular quantitative traits associated with this condition. This study examined the association of these loci with POAG, with central corneal thickness (CCT), vertical cup-to-disc ratio (VCDR) and with diabetes mellitus in a group of black South Africans (215 POAG cases and 214 controls). The population was homogeneous and distinct from other African and European populations. Single SNPs in the MYOC, CO ...[more]

PMID: 25669751

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Project description:Although appendicular skeletal muscle mass (ASM) and handgrip strength (HGS) are key components of sarcopenia, their underlying biological mechanisms remain poorly understood. We aimed to investigate associations of circulating biomarkers with ASM and HGS in middle-aged black South Africans. This study consisted of 934 black South Africans (469 men and 465 women, aged 41-72 years) from the Middle-aged Soweto cohort. Linear regression models were used to examine relationships between 182 biomarkers (measured with proximity extension assay) and dual-energy X-ray absorptiometry-measured ASM and dynamometer-measured HGS. Age, height, sex, smoking, alcohol, food insecurity, physical activity, visceral adipose tissue, HIV and menopausal status were included as confounders. Regression models showing sex-interactions were stratified by sex. The Benjamini-Hochberg false discovery rate (FDR) was used to control for multiple testing, and FDR-adjusted P values were reported. In the total sample, 10 biomarkers were associated with higher ASM and 29 with lower ASM (P < 0.05). Out of these 39 biomarkers, 8 were also associated with lower HGS (P < 0.05). MMP-7 was associated with lower HGS only (P = 0.011) in the total sample. Sex-interactions (P < 0.05) were identified for 52 biomarkers for ASM, and 6 for HGS. For men, LEP, MEPE and SCF were associated with higher ASM (P < 0.001, = 0.004, = 0.006, respectively), and MEPE and SCF were also associated with higher HGS (P = 0.001, 0.012, respectively). Also in men, 37 biomarkers were associated with lower ASM (P < 0.05), with none of these being associated with lower HGS. Furthermore, DLK-1 and MYOGLOBIN were associated with higher HGS only (P = 0.004, 0.006, respectively), while GAL-9 was associated with lower HGS only (P = 0.005), among men. For women, LEP, CD163, IL6, TNF-R1 and TNF-R2 were associated with higher ASM (P < 0.001, = 0.014, = 0.027, = 0.014, = 0.048, respectively), while IGFBP-2, CTRC and RAGE were associated with lower ASM (P = 0.043, 0.001, 0.014, respectively). No biomarker was associated with HGS in women. In conclusion, most biomarkers were associated with ASM and not HGS, and the associations of biomarkers with ASM and HGS displayed sex-specificity in middle-aged black South Africans. Proteomic studies should examine ASM and HGS individually. Future research should also consider sexual dimorphism in the pathophysiology of sarcopenia for development of sex-specific treatment and diagnostic methods.

Dataset Information

The genetics of POAG in black South Africans: a candidate gene association study.

Publications

The genetics of POAG in black South Africans: a candidate gene association study.

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