Role of genetic polymorphisms in factor H and MBL genes in Tunisian patients with immunoglobulin A nephropathy

Yousr Gorgi¹, Imen Hbibi¹, Imen Sfar¹, Tahar Gargueh², Majda Cherif³, Rim Goucha Louzir³, Raoudha Daghbouj ¹, Houda Aouadi¹, Mouna Makhlouf¹, Thouraya Ben Romdhane¹, Salwa Jendoubi-Ayed¹, Mohamed Amri¹, Adel Kheder³, Mohaled R Lakhoua², Taïeb Ben Abdallah¹, Khaled Ayed¹

¹Immunology Research Laboratory of Kidney Transplantation and Immunopathology (Laboratoire de recherche LR03SP01), Charles Nicolle Hospital, Tunisia; ²Pediatric department, Charles Nicolle Hospital, Tunisa; ³Nephrology Department, Charles Nicolle Hospital, Tunisa

Abstract: The molecular mechanisms of IgA nephropathy (IgAN) remain poorly understood. Several different polymorphic genes have been investigated in order to demonstrate their possible association with this disease. It is evident that mainly alternative and lectin pathways complement activation and play an important role in renal injury of IgAN. This study was conducted to determine eventual deficiencies of factor H in the SCR20 gene region and to look for a possible association between the polymorphism (+54) exon 1 of the MBL gene and the predisposition in Tunisian patients with IgAN. We then evaluated the effects of these FH mutations and/or this MBL polymorphism on nephropathy susceptibility and progression. Polymorphism A/B (+54) in the exon1 of the MBL gene and analysis within the C-terminal domain of the protein SCR20 in the exon 22 of the factor H (FH) gene were conducted in 36 sporadic IgAN Tunisian patients and 117 age and gender matched healthy subjects recruited from blood donors, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing respectively. The analysis of the Gly54Asp (+54) mutation of the MBL gene according to the criteria of gravity of the IgAN reveals that the patients with genotype AB present more frequently with end-stage renal disease (ESRD) compared with those of genotype AA [OR: 8, CI (1.74–54.49), P = 0.019]. Moreover, the variant allele B was statistically more frequent than the allele A in patients with an association with initial arterial high blood pressure, ESRD and class V of the Haas classification compared to those without this association (P =0.009). The direct sequencing of exon 22 (SCR 20) of FH gene did not reveal any abnormal mutational deficiency for this factor in all patients and controls. The data did not support the hypothesis that FH is a susceptibility factor for the IgAN. However the data did show there was an association between AB (+54) exon1 MBL genotype and severe sporadic forms of this disease in Tunisian patients. Because of the small number of subjects studied, a much larger cohort of IgAN patients with varying severity of the disease and its progression would seem necessary to confirm these findings.

Keywords: IgA nephropathy, genetics, factor H, MBL polymorphism, susceptibility