<i>TLR-8</i>, <i>TNF-α</i>, and <i>ESR-1α</i> Gene Polymorphism Susceptibility in Onset of Arthritis.

Arthritis is a genetic disorder characterized by bones and joint degradation assisted by severe pain and inflammation. It is evident by the studies that 0 candidate genes variations play vital role in its development and progression. Therefore, we investigated the genetic variation of <i>TLR-8</i>, <i>TNF</i>, and <i>ESR-1α</i> genes in the Pakistani population. A case-control study comprising 300 RA, 316 OA, and 412 control subjects was conducted. PCR-RFLP and direct sequencing methods were used for determining genetic variations. Analysis was performed by using PLINK and MEGA 6.0 software. Allelic and genetic frequencies of polymorphisms identified on rs3764879 (<i>TLR-8</i>), rs3764880 (<i>TLR-8</i>), rs5744080 (<i>TLR-8</i>), rs1800629 (<i>TNF</i>), rs2228480 (<i>ESR-1α</i>), and rs1451501590 (<i>ESR-1α</i>) were significantly varied among RA, OA, and controls. Novel functional mutations SCV000844945 and SCV000844946 on <i>TLR-8</i> as well as a non-functional SCV000804801 and functional variation SCV000804802 on <i>ESR-1α</i> were also identified and reported for the first time in the studied population. Multiple site analyses indicated that polymorphisms on <i>TLR-8</i> and <i>ESR-1α</i> genes were significant risk factors in disease onset to the next generation. In conclusion, <i>TLR-08</i> and <i>ESR-1α</i> were significant in the onset of arthritis whereas the <i>TNF</i> was not found as a significant risk factor in the onset of RA and OA.